bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality control for parasitologic data.
Authors: Cline B L , Habib M , Gamil F , Abdel-Aziz F , Little M D
Published: May 2017

Accuracy of data is of paramount concern for all research. The task of providing objective assurances of accuracy of parasitologic data for a large, multi-center epidemiologic research project in Egypt (Epidemiology 1, 2, 3 [EPI 1, 2, 3]) presented a unique set of challenges undertaken jointly by the Ministry of Health's Qalyub Center for Field and Applied Research with technical assistance from Tulane University (New Orleans, LA). The EPI 1, 2, 3 project was part of large bilateral research program, the Schistosomiasis Research Project, undertaken jointly by the governments of Egypt and the United States. This paper describes the nature of the quality control system developed to accomplish this task, presents results and discusses the findings.
Expression of proinflammatory cytokines in four regions of the brain in Macaque mulatta (rhesus) monkeys infected with Plasmodium coatneyi.
Authors: Tongren J E , Yang C , Collins W E , Sullivan J S , Lal A A , Xiao L
Published: May 2017

We have characterized brain cytokine expression profiles in the Plasmodium coatneyi/rhesus (Macaque mulatta) malaria model. Eight rhesus monkeys were included in the study; four were infected with P. coatneyi, and four were used as uninfected controls. All inoculated animals became infected. Eleven days after parasite inoculation, the rhesus monkeys were killed and tissue samples from 4 regions of the brain (cortex and white matter of the cerebrum, cerebellum, and midbrain) were collected for quantitation of mRNA expression of cytokines, adhesion molecules, and inducible nitric oxide synthetase (iNOS) by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression levels of tumor necrosis actor-alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-1-beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synethetase (iNOS) were highest in the cerebellum of infected animals, correlating well with pathologic observations of sequestration of parasitized erythrocytes in this region of the brain. Infected animals also had higher TNF-alpha expression levels in the cortex and IL-1beta expression levels in the cortex, white matter, and midbrain. Thus, the expression of pro-inflammatory and T helper-1 (TH-1) cytokines, adhesion molecules, and iNOS appears to predominate in the cerebellum of infected rhesus monkeys.
The potential impact of integrated malaria transmission control on entomologic inoculation rate in highly endemic areas.
Authors: Killeen G F , McKenzie F E , Foy B D , Schieffelin C , Billingsley P F , Beier J C
Published: May 2017

We have used a relatively simple but accurate model for predicting the impact of integrated transmission control on the malaria entomologic inoculation rate (EIR) at four endemic sites from across sub-Saharan Africa and the southwest Pacific. The simulated campaign incorporated modestly effective vaccine coverage, bed net use, and larval control. The results indicate that such campaigns would reduce EIRs at all four sites by 30- to 50-fold. Even without the vaccine, 15- to 25-fold reductions of EIR were predicted, implying that integrated control with a few modestly effective tools can meaningfully reduce malaria transmission in a range of endemic settings. The model accurately predicts the effects of bed nets and indoor spraying and demonstrates that they are the most effective tools available for reducing EIR. However, the impact of domestic adult vector control is amplified by measures for reducing the rate of emergence of vectors or the level of infectiousness of the human reservoir. We conclude that available tools, including currently neglected methods for larval control, can reduce malaria transmission intensity enough to alleviate mortality. Integrated control programs should be implemented to the fullest extent possible, even in areas of intense transmission, using simple models as decision-making tools. However, we also conclude that to eliminate malaria in many areas of intense transmission is beyond the scope of methods which developing nations can currently afford. New, cost-effective, practical tools are needed if malaria is ever to be eliminated from highly endemic areas.
Occurrence and self-treatment of diarrhea in a large cohort of Americans traveling to developing countries.
Authors: Hill D R
Published: May 2017

There is little information available regarding traveler's diarrhea that affects a large number of Americans who differ widely in age and travel destination, and little or no information exists on self-treatment. This paper describes the clinical features, self-treatment, and outcome of diarrhea in 784 (95% follow-up) Americans who traveled for < or = 90 days, and who received detailed pre-travel advice. Diarrhea was reported by 46%. Of these, 34% (n = 270) had traveler's diarrhea (TD) defined as > or = 3 unformed stools/day +/- enteric symptoms or < 3 stools/day with > or = 1 enteric symptom, and 11% (n = 88) had loose motions (LM). Diarrhea was often severe and nearly a quarter of people with TD experienced fever and vomiting and 35% were required to alter their plans. The duration of travel and the destination itself were the strongest influences on diarrhea. Most travelers treated the illness themselves, whether or not they had LM (72%) or TD (83%). Those with LM took an antimotility agent or bismuth subsalicylate alone more frequently than those with TD (71% versus 48%, P < 0.002). Conversely, antibiotics were taken more frequently by those with TD (47% versus 27%, P < 0.03). Overall, 83% indicated self-treatment was effective (91% with LM and 80% with TD). Diarrhea is common despite pre-travel advice. Because travelers usually treat themselves, they should be provided with clear instructions on appropriate self-treatment.
Assessing drug sensitivity of Plasmodium vivax to halofantrine or choroquine in southern, central Vietnam using an extended 28-day in vivo test and polymerase chain reaction genotyping.
Authors: Taylor W R , Doan H N , Nguyen D T , Tran T U , Fryauff D J , GÃ³mez-SaladÃ­n E , Kain K C , Le D C , Baird J K
Published: May 2017

Chloroquine-resistant Plasmodium vivax malaria is emerging in Oceania, Asia, and Latin America. We assessed the drug sensitivity of P. vivax to chloroquine or halofantrine in two villages in southern, central Vietnam. This area has chloroquine-resistant Plasmodium falciparum but no documented chloroquine-resistant P. vivax. Standard dose chloroquine (25 mg/kg, over 48 hours) or halofantrine (8 mg/kg, 3 doses) was administered to 29 and 25 patients, respectively. End points were parasite sensitivity or resistance determined at 28 days. Of the evaluable patients, 23/23 100% (95% confidence interval [CI] 85.1-100) chloroquine and 21/24 (87.5%) (95% CI 67.6-97.3) halofantrine-treated patients were sensitive. Three halofantrine recipients had initial clearance but subsequent recurrence of their parasitemias. Genotyping of the recurrent and Day 0 parasitemias differed, suggesting either new infections or relapses of liver hypnozoites from antecedent infections. Among these Vietnamese patients, P. vivax was sensitive to chloroquine and halofantrine. Genotyping was useful for differentiating the recurrent vivax parasitemias.
Xanthones as antimalarial agents: stage specificity.
Authors: Ignatushchenko M V , Winter R W , Riscoe M
Published: May 2017

The erythrocytic development of Plasmodium falciparum is divided into the ring, trophozoite, and schizont stages based on morphologic assessment. Using highly synchronous ring and trophozoite cultures of P. falciparum, we observed considerable differences in their sensitivity to hydroxyxanthones: trophozoites were much more sensitive to the drugs than ring-stage parasites. Trophozoites treated with a prototypic xanthone, the 2,3,4,5,6-pentahydroxy derivative (X5), were arrested in their development and became degenerate in appearance within 24 hr of drug exposure. These morphologic changes appeared to reflect the cytotoxic nature of the action of the drug against the parasite, since daughter ring-stage forms were not observed following addition of the drug. That X5 was more active against parasites in the later stages of intraerythrocytic development is consistent with the proposed mode of action, inhibition of heme polymerization. Knowledge of the structure-activity relationships for xanthones as antimalarial agents has also been expanded. Xanthones with a hydroxyl group in the peri-position exhibited decreased antimalarial activity, possibly due to intramolecular hydrogen bonding with the carbonyl and consequent reduced affinity for heme. Paired hydroxyls attached to the lower half of the xanthone greatly enhanced drug potency.
Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.
Authors: Pradines B , Spiegel A , Rogier C , Tall A , Mosnier J , Fusai T , Trape J F , Parzy D
Published: May 2017

The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71-50% inhibitory concentration (IC50) values for doxycycline ranged from 0.7 to 108.0 microM and the geometric mean IC50 for the 71 isolates was 11.3 microM (95% confidence interval = 9.5-13.4 microM). The activity of doxycycline did not differ significantly (P = 0.0858) between the chloroquine-susceptible isolates and the chloroquine-resistant isolates. There was no in vitro correlation between the responses to doxycycline and those to artemether, chloroquine, quinine, amodiaquine, pyrimethamine, and cycloguanil, suggesting no in vitro cross-resistance among these drugs. Potency was increased by prolonged exposure. In 96-hr incubations, the activity of doxycycline was 4-5-fold more increased than in 48-hr incubations. The in vitro activity of doxycycline against intraerythrocytic stages of multidrug-resistant P. falciparum, its action against the preerythrocytic forms, the lack of correlation between the responses in vitro of P. falciparum to doxycycline and the other antimalarial drugs, and its original potential site of action are factors that favor its use as antimalarial drug.
Placental changes associated with fetal outcome in the Plasmodium coatneyi/rhesus monkey model of malaria in pregnancy.
Authors: Davison B B , Cogswell F B , Baskin G B , Falkenstein K P , Henson E W , Krogstad D J
Published: May 2017

Term placentas collected surgically from seven Plasmodium coatneyi-infected rhesus monkeys, one abortion, and five controls were evaluated histopathologically. The placentas from Plasmodium-infected dams had more significant pathologic changes than those from controls for six parameters (P < 0.05) and higher numbers of activated (LN5 + Zymed) macrophages in the intervillous space (IVS) (P = 0.0173). Total parasite load (TPL) was defined as the sum of all weekly peripheral infected red blood cell counts for each trimester and for the entire pregnancy. High first trimester PLs were more likely to result in fetal demise (P = 0.0476) or increased placental damage in surviving infants. As trimester 2-3 TPL increased, so did the number of activated macrophages (P < 0.05) and the total malaria pigment scores (P < 0.05). Low birth weight (LBW) and intrauterine growth retardation (IUGR) were associated with high pigment scores and high numbers of activated macrophages in the IVS. High placental damage scores were not associated with IUGR, LBW, or early infant mortality.
Association between seropositivity of antibodies against hepatitis a virus and Helicobacter pylori.
Authors: Lin D B , Tsai T P , Yang C C , Wang H M , Nieh W T , Ling U P , Changlai S P , You S L , Ho M S , Chen C J
Published: May 2017

Helicobacter pylori and hepatitis A virus (HAV) are documented to share common transmission routes including fecal-oral. This study examined the association between seropositivity of antibodies against H. pylori (anti-HP) and HAV (anti-HAV) via a community-based survey of 40 randomly selected kindergartens in 10 urban and 10 rural areas. Serum samples from 2,047 healthy preschool children and 104 teachers were screened for anti-HP by enzyme-linked immunosorbent assay, and for anti-HAV by microparticle enzyme immunoassay. In children, a low prevalence of anti-HAV (0.44%) was found, in contrast to a high prevalence in their teachers (78.8%); anti-HP seroprevalence was 6.4% for children and 30.8% for teachers. Anti-HAV and anti-HP seropositivities were significantly associated in teachers after adjustment for age, sex, and residential area through multiple logistic regression analysis (multivariate-adjusted odds ratio = 7.3; 95% confidence interval [CI] = 1.4-36.8, P < 0.001). Our findings suggest that HAV and H. pylori may have shared transmission routes in central Taiwan 15 years or more ago, but not any recently.
Prevalence and genetic variants of hepatitis GB-C/HG and TT viruses in Gabon, equatorial Africa.
Authors: Tuveri R , Perret J L , Delaporte E , Nguemby-Mbina C , D'Allones L R , Henzel D , Faivre D , Scarpa B , Contu P , Colombo M , Thiers V , BrÃ©chot C , Larouze B
Published: May 2017

The distribution of Hepatitis GB-C/HG (GB-C/HG) and TT viruses (TTV) infections was investigated in selected populations from Gabon using Polymerase Chain Reaction (PCR) and Enzyme Linked Immunosorbent Assay (ELISA) for anti-Envelop 2 (anti-E2) GBV-C/HGV antibodies. Among pregnant women, 29 of 229 (12.6%) were Hepatitis GB virus-C and Hepatitis G virus (GBV-C/HGV) RNA positive (+) and 32 of 81 (39.5%) anti-E2 + versus 8 of 39 (20.5%) TTV DNA +. Among sickle cell anemia patients, 9.7% (3/31) were GBV-C/HGV RNA + versus 22.5% (7/31) TTV DNA +. For tuberculosis patients, the figures were 11.5% (4/35) and 0%. A study of hepatocellular carcinoma cases (n = 27) versus controls (n = 66) did not show significant differences for GBV-C/HGV RNA (10.7% versus 12.1%) and TTV DNA (44.4% versus 30.3%). According to phylogenetic analysis, the 15 GBV-C/HGV strains investigated clustered in group 1, the most common in sub-Saharan Africa whereas TTV sequences (n = 4) mostly clustered in genotypes G1 and one close to genotype G3. In the Gabonese populations investigated, GBV-C/HGV and TTV infections were highly endemic. These data are consistent with the low pathogenicity of these agents.
Risk factors associated with leptospirosis in northeastern Thailand, 1998.
Authors: Tangkanakul W , Tharmaphornpil P , Plikaytis B D , Bragg S , Poonsuksombat D , Choomkasien P , Kingnate D , Ashford D A
Published: May 2017

Leptospirosis is a zoonotic disease of worldwide distribution caused by spirochetes of the genus Leptospira. Humans are infected through direct contact with infected animals or through exposure to fresh water or soil contaminated by infected animal urine. Leptospirosis is characterized by acute fever that can be followed by a more severe, sometimes fatal illness that may include jaundice and renal failure (Weil's disease), meningitis, myocarditis, hemorrhagic pneumonitis, or hemodynamic collapse. To identify potential risk factors for leptospirosis in Thailand, we conducted a matched case-control study in Nakornratchasrima Province of the northeastern region. Fifty-nine cases and 118 controls were included in the study. Four activities in the two weeks prior to illness were independently associated with leptospirosis infection: walking through water (odds ratio [OR] = 4.9, 95% confidence interval [CI] = 1.7-14.1), applying fertilizer in wet fields for more than 6 hr a day (OR = 3.4, 95% CI = 1.5-7.8), plowing in wet fields for more than 6 hr a day (OR = 3.5, 95% CI = 1.1-11.6), and pulling out rice plant sprouts in wet fields for more than 6 hr a day (OR = 3.1, 95% CI = 1.02-9.3). Identification of these risk factors on admission might prove useful for early diagnosis and treatment of leptospirosis in Thailand.
Molecular epidemiology of malaria in Yaounde, Cameroon. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria.
Authors: Basco L K , Ringwald P
Published: May 2017

In an endemic area where malaria transmission is intense and continuous, reappearance of asexual parasites may be ascribed to either recrudescence or reinfection. To distinguish between recrudescence and reinfection after oral treatment with chloroquine, amodiaquine, pyronaridine, sulfadoxine-pyrimethamine, halofantrine, or artesunate, three polymorphic markers (circumsporozoite protein, merozoite surface antigens 1 and 2) from pre-treatment and post-treatment samples were amplified by the polymerase chain reaction, and the in vitro response to chloroquine was determined for comparison. Of 52 paired samples, 22 (42%) were reinfections. Recrudescence occurred more frequently on or before Day 14 (22 of 30 cases, 73%). Except for one case, all reinfections were observed beyond Day 14. The phenotype determination was not sufficiently precise to distinguish between recrudescence and reinfection. Our results suggest that beyond Day 14 (and until Day 42), recrudescence and reinfection cannot be distinguished at our study site unless molecular techniques are used and that some results derived from the polymerase chain reaction need to be compared with the microscopic examination of thick blood smear to exclude gametocyte carriers without asexual parasites after treatment.
Hepatitis C in Peru: risk factors for infection, potential iatrogenic transmission, and genotype distribution.
Authors: Sanchez J L , Sjogren M H , Callahan J D , Watts D M , Lucas C , Abdel-Hamid M , Constantine N T , Hyams K C , Hinostroza S , Figueroa-Barrios R , Cuthie J C
Published: May 2017

A large seroepidemiologic and genotyping study of hepatitis C virus (HCV) was conducted in Lima, Peru, during the periods of 1986 to 1993 (cohort A) and 1994 (cohort B). Anti-HCV seroprevalence rates were 15.6% (216 of 1,389) and 11.7% (168 of 1,438), respectively. Low rates were seen among volunteer blood donors (1.1% and 0.8%). Anti-HCV rates were much higher among patients undergoing hemodialysis (43.7% and 59.3%), hemophiliacs (60.0% and 83.3%), in those more than 39 years old (18.2% and 26.0%), in females (25.0% and 27.4%), and in less-educated persons (16.9%). Age- and gender-adjusted risk factors in cohort B included blood transfusion history (adjusted odds ratio [AOR] = 29.8), prior organ transplantation (AOR = 9.1) or a history of hepatitis (AOR = 4.9), previous hospitalization (AOR = 3.7), a history of intravenous drug use (AOR = 3.5), prior major surgery (AOR = 2.6), a history of acupuncture (AOR = 2.1), previous dental procedures (AOR = 1.2), and prior medical injections (AOR = 1.04). The most prevalent HCV genotype was type 1 (86%), followed by type 3 (10%) and type 2 (2%). Transmission through unsafe injection-related and medical/dental procedures appears to play an important role in HCV infection among Peruvians.
Pirital virus (Arenaviridae) infection in the syrian golden hamster, Mesocricetus auratus: a new animal model for arenaviral hemorrhagic fever.
Authors: Xiao S Y , Zhang H , Yang Y , Tesh R B
Published: May 2017

Adult Syrian golden hamsters inoculated intraperitoneally with Pirital virus, a recently discovered member of the Tacaribe complex of New World arenaviruses, developed a progressively severe, fatal illness with many of the pathologic features observed in fatal human cases of Lassa fever and other arenaviral hemorrhagic fevers. Most of the animals became moribund by Day 5 and were dead by Day 7 after inoculation. The most consistent histopathologic changes included interstitial pneumonitis, splenic lymphoid depletion and necrosis, and multifocal hepatic necrosis without significant inflammatory cell infiltration. The liver changes ranged from single cell death by apoptosis to coagulative necrosis of clusters of hepatocytes. Immunohistochemical studies of the liver demonstrated the presence and accumulation ot Pirital virus antigen within hepatocytes as well as Kupffer cells. An in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay showed progressively increasing apoptotic activity in the liver of infected hamsters. A human hepatoblastoma cell line (Hep G2/C3A) inoculated with Pirital virus also developed progressive cell destruction and accumulation of viral antigen, as demonstrated by immunofluorescence. Results of this pilot study suggest that the Pirital virus-hamster model is a very promising new small animal model for studying the pathogenesis of arenavirus infections, particularly, the mechanism of direct virus-induced hepatic injury. It may also be useful for testingantiviral agents for treatment of arenaviral hemorrhagic fevers.
Cost-effectiveness of sulfadoxine-pyrimethamine for the prevention of malaria-associated low birth weight.
Authors: Wolfe E B , Parise M E , Haddix A C , Nahlen B L , Ayisi J G , Misore A , Steketee R W
Published: May 2017

Prevention of placental malaria through administration of antimalarial medications to pregnant women in disease-endemic areas decreases the risk of delivery of low birth weight (LBW) infants. In areas of high Plasmodium falciparum transmission, two intermittent presumptive treatment doses of sulfadoxine-pyrimethamine (SP) during the second and third trimesters of pregnancy are effective in decreasing the prevalence of placental malaria in human immunodeficiency virus (HlV)-negative women, while HIV-positive women may require a monthly SP regimen to reduce their prevalence of placental parasitemia. A decision-analysis model was used to compare the cost-effectiveness of three different presumptive SP treatment regimens with febrile case management with SP in terms of incremental cost per case LBW prevented. Factors considered included HIV seroprevalence, placental malaria prevalence, LBW incidence, the cost of SP, medical care for LBW infants, and HIV testing. For a hypothetical cohort of 10,000 pregnant women, the monthly SP regimen would always be the most effective strategy for reducing LBW associated with malaria. The two-dose SP and monthly SP regimens would prevent 172 and 229 cases of LBW, respectively, compared with the case management approach. At HIV seroprevalence rates greater than 10%, the monthly SP regimen is the least expensive strategy. At HIV seroprevalence rates less than 10%, the two-dose SP regimen would be the less expensive option. When only antenatal clinic costs are considered, the two-dose and monthly SP strategies cost US $11 and $14, respectively, well within the range considered cost effective. Presumptive treatment regimens to prevent LBW associated with malaria and the subsequent increased risk of mortality during the first year of life are effective and cost effective strategies in areas with both elevated HIV prevalence and malaria transmission rates.
Diagnosis of imported malaria by Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein 2 (PfHRP-2)-based immunocapture assays.
Authors: Iqbal J , Hira P R , Sher A , Al-Enezi A A
Published: May 2017

This study was conducted to evaluate the performance of two rapid non-microscopic assays: Plasmodium lactate dehydrogenase (pLDH) assay (OptiMAL) and Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) assay (ICT Malaria). The assays were used to detect malaria infection in 515 immigrants living in Kuwait. The performance of both assays was compared to that of microscopy of Giemsa-stained thick blood films and to each other. Of the 515 patients tested, 163 were positive for malaria parasites by microscopy of thick blood film. Of these, 87 were infected with Plasmodium vivax parasites, 63 with P. falciparum, 1 with Plasmodium malariae, and 12 had mixed infections of P. falciparum and P. vivax. The PfHRP-2 assay detected 53 P. falciparum infections and, as expected, failed to detect all but one case of P. vivax. Three cases of mixed infections were also not detected by this assay. The pLDH assay detected 56 P. falciparum cases and 77 P. vivax infections but failed to detect 4 cases of mixed infections. Compared to microscopy, the performance of both the assays to diagnose P. falciparum infection was comparable. The sensitivity for the PfHRP-2 assay was 82% with a specificity of 99.0% and for the pLDH assay the sensitivity was 89% with a specificity of 99.5%. The PfHRP-2 assay detected 4 false positive cases, 2 of which were also detected by the pLDH assay. These patients reported treatment with chloroquine in the last 2-5 weeks. Though the immunocapture diagnostic assays may be helpful in certain situations, microscopy of thick blood film is still the method of choice in diagnosing imported malaria.
A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.
Authors: LefÃ¨vre G , Looareesuwan S , Treeprasertsuk S , Krudsood S , Silachamroon U , Gathmann I , Mull R , Bakshi R
Published: May 2017

The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem/Riamet; Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (> or = 12 years old) with acute, uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] = 91.7, 97.9%) for artemether-lumefantrine and 100% (90% CI = 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse events were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups showed QTc prolongations but without any cardiac complication, and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen, and were higher, particularly for lumefantrine, than those previously observed with the four-dose regimen, explaining the greater efficacy of the six-dose regimen in a drug-resistant setting. These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria.
Hemoglobin concentration in children in a malaria holoendemic area is determined by cumulated Plasmodium falciparum parasite densities.
Authors: Ekvall H , Premji Z , Bennett S , Bjorkman A
Published: May 2017

In malaria holoendemic areas children are anemic, but the exact influence of falciparum malaria on hemoglobin (Hb) concentration remains largely unsettled. Prospective data were therefore collected in children < 24 months of age during five months in a Tanzanian village. Children with mean asymptomatic parasitemia > or = 400/microl had lower median Hb levels during the study than those with mean density < 400/microl. The difference was 9.7 g/L (95% confidence interval [CI] 2.8-17). In children with one or more clinical malaria episodes, the median Hb was 8.3 g/L (95% CI 0.9-16) lower than those without episode. If early treatment failure was recorded, the immediate effect on Hb was particularly important with a mean drop of 17 g/L. Interestingly, at study-end the Hb concentration represented a function of the area under the parasitemia curve (AUPC) during the previous five months, adjusting for age. In conclusion, stepwise deterioration in median Hb levels was found by asymptomatic parasitemia, clinical malaria episode, and most significantly, treatment failure.
Short report: increased susceptibility to Plasmodium malariae in pregnant alpha(+)-thalassemic women.
Authors: Mockenhaupt F P , Rong B , Till H , Thompson W N , Bienzle U
Published: May 2017

The influence of alpha(+)-thalassemia on malaria in pregnancy was assessed in a cross-sectional study of 530 women in Ghana. Plasmodial infections, alpha(+)-thalassemia, serum levels of C-reactive protein, and antimalarial drugs in urine were determined. The alpha-globin genotypes did not correlate with the prevalence of Plasmodium falciparum-infection and parasite densities. However, Plasmodium malariae tended to be more frequent in alpha(+)-thalassemic women (P = 0.05). Excluding women with residual antimalarials, a significant excess of P. malariae was observed in alpha(+)-thalassemic individuals. Febrile responses (P = 0.05) and inflammation (CRP > 0.6 mg/dl, P = 0.06) appeared to be less common in infected alpha(+)-thalassemic women and were also comparatively rare in parasitemic individuals who harbored double species infections with P. falciparum and P. malariae. Plasmodium malariae may influence the pathogenesis of falciparum malaria leading to a low prevalence of inflammation and febrile responses in alpha(+)-thalassemic women.
In vitro antimalarial activity of extracts of three plants used in the traditional medicine of India.
Authors: Bhat G P , Surolia N
Published: May 2017

In an attempt to search for new antimalarial drugs, we studied plants used by traditional healers of southwest India to treat malaria. Aqueous and organic solvent extracts obtained from specific parts of the plants Swertia chirata, Carica papaya, and Citrus sinensis were tested on malaria strain Plasmodium falciparum FCK 2 in vitro. The temperatures of extraction were the same as that used by the traditional healers in their plant preparations. Visual evaluation of the antimalarial activity of the plant extracts on thin blood smears was followed by quantification of the activity by use of [35S]-methionine incorporation into parasite proteins to determine the value that inhibits 50% (IC50). Among the 3 plants tested, 2 had significant inhibitory effect on P. falciparum in vitro.
The value of an immunoenzymatic test (enzyme-linked immunosorbent assay) for the diagnosis of strongyloidiasis in patients immunosuppressed by hematologic malignancies.
Authors: Schaffel R , Nucci M , Carvalho E , Braga M , Almeida L , Portugal R , Pulcheri W
Published: May 2017

The diagnosis of strongyloidiasis relies upon the identification of the parasite in stool samples. In 1981, a serologic assay was developed, which was useful in the diagnosis of strongyloidiasis in the immunocompetent host. In the present study, we evaluated the enzyme-linked immunosorbent assay (ELISA) in patients with hematologic malignancies. Between April 1995 and December 1998, sera from 164 consecutive patients were tested for the presence of IgG antibody to Strongyloides stercoralis. Patient was considered uninfected after at least three negative stool examinations. The prevalence of strongyloidiasis was 13%. The underlying diseases were acute leukemia in 21% and lymphoma in 52% of the patients. The majority of the patients were receiving chemotherapy (93%) and steroids (76%). The sensitivity, specificity, and positive and negative predictive values were 68%, 89%, 48%, and 95%, respectively. The ELISA may be an excellent assay to rule out the diagnosis of strongyloidiasis in patients with hematologic malignancies.
Replication of dengue virus type 2 in human monocyte-derived macrophages: comparisons of isolates and recombinant viruses with substitutions at amino acid 390 in the envelope glycoprotein.
Authors: Pryor M J , Carr J M , Hocking H , Davidson A D , Li P , Wright P J
Published: May 2017

The severity of dengue virus infection ranges from mild fever to dengue hemorrhagic fever and shock syndrome. The association of disease severity with virus replication in monocyte-derived macrophages (MDMs) was examined for dengue virus type 2 (DEN-2) isolates from Asia or America. Additionally, we constructed DEN-2 recombinant viruses with substitutions at residue 390 in the envelope glycoprotein (E390) because this residue is linked with the region of virus origin. Comparisons of virus yields of 3 isolates failed to show a correlation with clinical disease. However, the American strain did not replicate as well as the 2 Asian strains. For the recombinant viruses, substitution of Asn (Asian) at E390 with Asp (American) resulted in decreased ability to replicate in MDMs. These results are consistent with the proposal that the lack of association of native American DEN-2 strains with severe disease is linked to reduced ability to replicate in MDMs, and that Asp at E390 may contribute to this reduction.
Comparative pharmacokinetics and effect kinetics of orally administered artesunate in healthy volunteers and patients with uncomplicated falciparum malaria.
Authors: Teja-Isavadharm P , Watt G , Eamsila C , Jongsakul K , Li Q , Keeratithakul G , Sirisopana N , Luesutthiviboon L , Brewer T G , Kyle D E
Published: May 2017

The single-dose pharmacokinetics of 100 mg of orally administered artesunate (AS) were studied in 6 patient volunteers with uncomplicated falciparum malaria and in 6 healthy volunteers. Plasma concentrations of both the parent drug, AS, and its major metabolite, dihydroartemisinin (DHA), were measured simultaneously by high-performance liquid chromatography (HPLC) with electrochemical detection (ECD). The antimalarial activity of each plasma sample measured by an in vitro bioassay (BA) was used to derive activity concentrations. Artesunate was absorbed rapidly and then almost completely hydrolyzed to DHA in patients, whereas hydrolysis was incomplete in healthy volunteers. The mean +/- standard deviation (SD) maximum concentration (Cmax) of AS was 296+/-110 nmol/L, the time to peak blood level (tmax was 0.71+/-0.66 hr, the half-life (t1/2,z) was 0.41+/-0.34 hr, and the bioavailability over 12 hr (area under the curve [AUC](0-12)) was 253+/-185 nmol hr/L. Measured by HPLC, the Cmax and AUC(0-12) values of DHA in patients with malaria were significantly greater than in volunteers (1,948+/-772 and 1,192+/-315 nmol/L; 4,024+/-1,585 and 1,763+/-607 nmol hr/L, respectively; P < or = 0.05). These differences were even greater when measured by BA. The Cmax for patients with malaria was 2,894+/-2,497 and 795+/-455 nmol/L for volunteers, and AUC(0-12) was 5,970+/-3,625 and 1,307+/-391 nmol hr/L, respectively (P < or = 0.05). In contrast, DHA parameter estimates for t1/2,z and tmax were similar between patients and healthy volunteers, with values of 0.80+/-0.30 versus 0.87+/-0.06 hr and 1.50+/-0.55 versus 1.13+/-0.52 hr, respectively (P > 0.5). Both drug metabolism and tissue protein binding could contribute to the differences between the antimalarial activity of artemisinin drugs in healthy volunteers and malaria infected patients.
Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever.
Authors: Cam B V , Fonsmark L , Hue N B , Phuong N T , Poulsen A , Heegaard E D
Published: May 2017

We present a prospective case-control study of 27 serologically confirmed dengue hemorrhagic fever (DHF) patients with severe central nervous system symptoms. Dengue associated encephalopathy accounted for 0.5% of 5,400 patients admitted with DHF. The mortality rate among children with encephalopathy was 22%, with the survivors experiencing a complete recovery. Liver enzymes and bilirubin were significantly elevated in the study group. In analysis of the cerebrospinal fluid (CSF), reverse transcriptase-polymerase chain reaction revealed dengue-3-specific RNA in one evaluated case. Dengue-specific immunoglobulin M was detected in CSF in 14 of 22 assessable patients, indicating a localized infection. Magnetic resonance imaging scans showed cerebral edema in the majority of patients, although encephalitis-like changes were less common. There was an equal distribution of primary and secondary infections. On the basis of previous reports and of the findings of our study, DHF probably encompasses an expanding clinical spectrum that infrequently involves encephalitis due to a direct neurotropic effect of dengue virus.
Factors influencing the use of bed nets in Mbarara municipality of Uganda.
Authors: Nuwaha F
Published: May 2017

In order to identify independent predictors for bed net use, respondents from 643 households selected randomly from 21 clusters were interviewed in Mbarara municipality, Uganda. Respondents answered questions about demographic characteristics, social economic conditions, causes and transmission of malaria, beliefs about severity and complications of malaria, malaria morbidity and health care-seeking behavior, perceived control of malaria prevention, beliefs about utility of bed nets, perceived susceptibility to malaria, and whether they use bed nets or not. Univariate and multivariate logistic regression analyses were used to identify predictors for bed net use. Fifty-five percent (356 of 643) of the households had bed net users. The independent factors that favored bed net use were as follows: 1) age < 30 years, 2) ownership of a television, 3) having mosquito nets in ventilators of the house, 4) being a skilled worker or a professional, or owning a major business, 5) living in a permanent house, 6) believing that bed nets prevent malaria, 7) believing that bed nets are worth their cost, 8) not believing that convulsions cannot be cured by modern medicine, and 9) believing that bed nets are not expensive. The strongest predictors of bed net use are living in a permanent house and agreeing that bed nets are worth their cost, with adjusted odds ratios of 4.29 (95% confidence interval, 2.76-6.71) and 3.93 (95% confidence interval, 2.5-26.13), respectively. These data suggest that in order to increase the use of bed nets, the price of bed nets needs to be reduced and educational messages that stress the favorable use of bed nets need to be increased.
Simple form of clinical sample preservation and Leishmania DNA extraction from human lesions for diagnosis of American cutaneous leishmaniasis via polymerase chain reaction.
Authors: Marques M J , Volpini A C , Genaro O , Mayrink W , Romanha A J
Published: May 2017

The diagnosis value of polymerase chain reaction (PCR) was assessed in patients from an area endemic for American cutaneous leishmaniasis (ACL) in Brazil. Different forms of clinical sample preservation and DNA extraction for PCR were tested. The 4 preservation forms of the skin biopsies from patients suspected to have ACL were as follows: imprinted on filter paper (FP); imprinted on nitrocellulose paper (NP); frozen at -20 degrees C (FB); or immersed in 70% ethanol (EB). The DNA was extracted by elution from FP and NP and by enzyme digestion from FB and EB. Clinical examinations and parasitological or immunological tests confirmed the cases of ACL. Of 164 patients suspected to have ACL, 133 patients (81.1%) were confirmed. The PCR was positive in 76.8% of the suspected cases and in 90.2% of the confirmed cases. Polymerase chain reaction alone showed nearly the same positivity of the parasitological and immunological tests together; positivity varied 73.3-82.2%, according to the means by which the samples were preserved or the way the DNA was extracted. This variation was not significantly different (P > 0.05). Therefore, we recommend that clinical samples from patients with ACL should be collected and preserved on FP and the DNA further extracted by elution. The samples can be mailed to reference laboratories for the definitive diagnosis of ACL. This alternative is simple, inexpensive, and adequate for field conditions in developing countries.
Family analysis of malaria infection in Dienga, Gabon.
Authors: Domarle Olivier , Migot-Nabias Florence , Pilkington Hugo , Elissa Nohal , TourÃ© Fousseyni S , Mayombo Justice , Cot Michel , Deloron Philippe
Published: May 2017

Fifty children from 9 families were enrolled in a longitudinal study of 8 months to evaluate individual levels of Plasmodium falciparum density in blood during asymptomatic infections. Individual parasite densities were adjusted for age and date of blood intake. The arithmetic means of these adjusted parasite densities (MAPD) were not influenced by sickle cell trait nor by G6PD enzyme activity. On the contrary, family analysis revealed the presence of similar MAPD values according to the sibships. Moreover, sibships frequently infected with P. malariae exhibited the highest P. falciparum MAPDs. The difference in aggressiveness of malaria vectors between the northern and southern halves of the village did not explain the distribution of MAPD, nor did it explain the differences in mean frequency of P. malariae infection among the sibships. We conclude that the familial characteristic of susceptibility to both P. falciparum and P. malariae infections is more likely influenced by the host's genetic background than by differences in the levels of malaria transmission.
Serological evidence for recent exposure to Taenia solium in Venezuelan Amerindians.
Authors: Ferrer E , Cortez M M , Perez H , De la Rosa M , de Noya B Alarcon , D'Avila I , Harrison L J S , Foster-Cuevas M , Parkhouse R M E , Cabrera A
Published: May 2017

This study examined the seroprevalence and serum antibody isotype profile for Taenia solium cysticercosis in an Amerindian community in the Amazonas state of Venezuela. An antigen-trapping enzyme-linked immunosorbent assay (Ag-ELISA) was used to detect viable cysticercosis. Indirect ELISA (Ab-ELISA) and enzyme-linked immunoelectrotransfer blot (EITB) was performed by using antigens prepared from T. solium metacestodes to detect anti-parasite antibodies. The Ag-ELISA and Ab-ELISAs revealed 64.7% and 79.0% seropositivity, respectively, in the Amerindian population. Immunoglobulin (Ig) M was the predominant antibody class, suggesting recent infection. In comparison sera from, clinically defined, hospital neurocysticercosis cases revealed only 27% seropositivity by Ag-ELISA, compared with 86-92% seropositivity by Ab-ELISA, and IgG4 was the predominant antibody subclass detected. The EITB antigen recognition patterns of the hospitalized patients were very similar to that of the Amerindians, confirming exposure to the parasite. These results, combined with the predominance of IgM antibody responses and the marked detection of secreted products of viable parasites, strongly suggest that recent exposure to T. solium had occurred in the Amerindian population.
Emergence of a new neotropical malaria vector facilitated by human migration and changes in land use.
Authors: Conn Jan E , Wilkerson Richard C , Segura M NazarÃ© O , de Souza Raimundo T L , Schlichting Carl D , Wirtz Robert A , PÃ³voa Marinete M
Published: May 2017

In a region of northeastern Amazonia, we find a species previously of minor importance, Anopheles marajoara, to be the principal malaria vector. In a total of five collections during 1996-97 in three replicated sites near the city of MacapÃ¡, AmapÃ¡ state, this species occurs in much greater abundance compared with the presumed vector Anopheles darlingi. Also, a significantly higher proportion of An. marajoara is infected with malaria parasites, determined by the ELISA technique. This appears to be the result of increased abundance of An. marajoara due to alterations in land use, invasion of its primary breeding sites by human immigrants, and its anthropophilic behavior. This discovery highlights one of the challenges of Neotropical malaria control, namely that the targeting of specific vectors may be complicated by a changing mosaic of different locally important vectors and their interactions with human populations.
Etiology of encephalitis syndrome among hospitalized children and adults in Takeo, Cambodia, 1999-2000.
Authors: Srey Viseth Horm , Sadones Helene , Ong Sivuth , Mam Mony , Yim Chantham , Sor Sokhom , Grosjean Pierre , Reynes Jean-Marc
Published: May 2017

Whether or not Japanese encephalitis virus (JEV) is an important causative agent of acute encephalitis in Cambodia remains unclear. This study was carried out to determine the cause of encephalitis syndrome among children and adults admitted to Takeo Provincial Hospital from October 1999 to September 2000. Ninety-nine cases were included in the study: 52 pediatric cases (12 were fatal) and 47 adult cases (10 were fatal). A causative agent such as human herpesvirus (HHV-3 or HHV-4), Cryptococcus neoformans, or Mycobacterium tuberculosis had been identified in 8 of the 11 adults who had human immunodeficiency virus type 1 (HIV-1). An infectious agent was identified in 35 (40%) of 88 HIV-1-seronegative patients (60% of the causes remains unidentified). These comprised 11 bacterial infections, 1 fungal infection, and 23 viral infections. The viral infections were 1 fatal HHV-4 infection, 5 dengue virus infections (2 fatal), 1 coinfection with flavivirus and alphavirus, and 16 presumptive infections JEV (no virus detected), one case of which was fatal. Infection with JEV, the principal cause identified in the 99 encephalitis syndromes, concerned 16 (31%) of 52 children.
Breeding structure of Aedes aegypti populations in Mexico varies by region.
Authors: Gorrochotegui-Escalante Norma , Gomez-Machorro Consuelo , Lozano-Fuentes Saul , Fernandez-Salas Lldefonso , De Lourdes Munoz Maria , Farfan-Ale Jose A , Garcia-Rejon Julian , Beaty Barry J , Black William C
Published: May 2017

A population genetic analysis of Aedes aegypti was conducted among 38 collections from throughout coastal regions of Mexico. Multiple collections were made within 5 cities to examine local patterns of gene flow. Single-strand conformation polymorphism analysis was used to screen for variation in a 387-bp region of the Nicotinamide Adenine Dinucleotide Dehydrogenase subunit 4 mitochondrial gene (ND4) and 25 haplotypes were detected. Northeastern Mexico collections were genetically differentiated from and had lower genetic diversity than Yucatan and Pacific coastal collections. Yucatan and Pacific collections were genetically homogeneous. Regression analysis of geographic distances and F(ST) values indicated that collections were genetically isolated by distance in the Pacific and the Yucatan, but not among collections in the northeast. Free gene flow occurred among all collections within 130 km of one another in the northeast and within 180 km in the Yucatan. F(ST) values were never large among Pacific collections, suggesting extensive gene flow along the Pacific coast.
Low cellular response in vitro among subjects with long-term exposure to malaria transmission in Brazilian endemic areas.
Authors: Braga Erika M , Carvalho Luzia H , Fontes Cor J F , Krettli Antoniana U
Published: May 2017

The cellular and humoral immune responses to Plasmodium falciparum and P. vivax recombinant circumsporozoite (rCS) proteins were studied in two populations in the Brazilian malaria-endemic region. One group of subjects lived in an urban area that was free from the risk of malaria and was exposed to the disease through short visits to the endemic area. The other group had lived for approximately 10 years in a rural area, where they were continuously exposed to transmission. Proliferative responses to rCS proteins were observed in 50% of 16 adults not continuously exposed to malaria but in only five of 48 subjects (10%) resident in the transmission area. The antibody responses to rCS proteins were approximately 50% in both groups. The interferon-gamma (IFN-gamma) response evaluated only among continuously exposed subjects was low. There was no association between the presence of antibodies and the detection of proliferative or IFN-gamma T cell responses. These findings suggest that continuous exposure to malaria in areas of low endemicity may lead to a specific decrease of the in vitro T cell function.