bluuebunny/crossref_metadata_2025 huggingface dataset:
Q FEVER IN CHILDREN IN GREECE
Authors: MALTEZOU HELEN C. , CONSTANTOPOULOU IOANNA , KALLERGI CONSTANTINA , VLAHOU VASILIKI , GEORGAKOPOULOS DIMITRIS , KAFETZIS DIMITRIS A. , RAOULT DIDIER
Published: September 2018

The aim of this study was to investigate the incidence, epidemiology, and clinical manifestations of Q fever among hospitalized children in Greece. During a two-year period, 1,200 children with various clinical manifestations were prospectively tested for Coxiella burnetii infection by indirect immunofluorescence. Acute Q fever was diagnosed in eight (0.67%) patients. No chronic case of infection was detected. Multivariate analysis showed that children 11–14 years old and children reporting consumption of cheese from rural areas were at increased risk for this illness. Clinical manifestations of acute Q fever were pneumonia (two patients), meningitis (two), prolonged fever (two), hepatitis (one), and hemolytic-uremic syndrome (one). Q fever accounted for 2.9% of the cases with prolonged fever, 1.2% of the cases of meningitis, and 0.5% of the cases of pneumonia. Fever and headache were the most common symptoms at presentation. Our study indicates that Q fever is a rare cause of hospitalization during childhood.
LOW HERITABLE COMPONENT OF RISK FOR INFECTION INTENSITY AND INFECTION-ASSOCIATED DISEASE IN URINARY SCHISTOSOMIASIS AMONG WADIGO VILLAGE POPULATIONS IN COAST PROVINCE, KENYA
Authors: KING CHARLES H. , BLANTON RONALD E. , MUCHIRI ERIC M. , OUMA JOHN H. , KARIUKI H. CURTIS , MUNGAI PETER , MAGAK PHILIP , KADZO HILDA , IRERI EDMUND , KOECH DAVY K.
Published: September 2018

To estimate their heritable component of risk for Schistosoma haematobium infection intensity and disease, we performed a community-based family study among an endemic population in coastal Kenya. Demography and family linkages were defined by house-to-house interviews, and infection prevalence and disease severity were assessed by standard parasitologic testing and by ultrasound. The total population was 4,408 among 912 households, with 241 identified pedigree-household groups. Although age- and sex-adjusted risk for greater infection intensity was clustered within households (odds ratio = 2.7), analysis of extended pedigree-household groups indicated a relatively low heritability score for this trait (h2 = 0.199), particularly after adjustment for common household exposure effects (adjusted h2 = 0.086). Statistical evidence was slightly stronger (h2 = 0.353) for familial clustering of bladder morbidity, with an adjusted h2 = 0.142 after accounting for household exposure factors. We conclude that among long-established populations of coastal Kenya, heritable variation in host susceptibility is low, and likely plays a minimal role in determining individual risk for infection or disease.
RELATIONSHIP OF GENOTYPE RATHER THAN RACE TO HEPATITIS B VIRUS PATHOGENICITY: A STUDY OF JAPANESE AND SOLOMON ISLANDERS
Authors: FURUSYO NORIHIRO , KUBO NORIHIKO , NAKASHIMA HISASHI , KASHIWAGI KENICHIRO , HAYASHI JUN
Published: September 2018

The aim of this study was to determine the predominant hepatitis B virus (HBV) genotype in the Solomon Islands and determine if there is any racial correlation between genotype and hepatitis B e antigen (HBeAg) production in Japanese and Melanesian individuals. A total of 403 serum samples from 206 Melanesian HBV carriers in the Solomon Islands and 197 Japanese carriers from Fukuoka (n = 106) and Okinawa (n = 91) living in Japan in 2001 were tested. The HBV genotypes of 206 Melanesian subjects were 114 with genotype C (55.3%) and 92 with genotype D (44.7%). The HBV genotypes of 197 Japanese subjects were 74 with genotype B (37.6%) and 123 with genotype C (62.4%). The total HBeAg prevalence of subjects in Fukuoka (36.8%) was significantly higher than that of subjects in Okinawa (14.3%) (P < 0.0001) and subjects in the Solomon Islands (35.0%; P = 0.0014, by the Mantel-Haenszel test). The genotype C prevalences were significantly different, ranging from 24.2% in Okinawa, to 54.4% in the Solomon Islands, to 95.3% in Fukuoka (all P < 0.0001, by chi-square test). The prevalence of HBeAg positivity was significantly higher in Melanesian genotype C subjects (42.0%) than Melanesian genotype D subjects (26.6%) (P = 0.0310). Similarly, the prevalence of HBeAg positivity was significantly higher in Japanese genotype C subjects (36.6%) than Japanese genotype B subjects (9.5%) (P < 0.0001). These findings indicate that that HBV was of genotypes C and D in the Solomon Islands, and that the pathogenesis of HBV-infected patients is related to HBV genotype rather than race.
COMPARISON OF THE EFFECTIVENESS OF FIVE DIFFERENT ANTIBIOTIC REGIMENS ON INFECTION WITH RICKETTSIA TYPHI: THERAPEUTIC DATA FROM 87 CASES
Authors: GIKAS ACHILLEAS , DOUKAKIS STEPHANOS , PEDIADITIS JOHN , KASTANAKIS SERAFIM , MANIOS ANDREAS , TSELENTIS YIANNIS
Published: September 2018

This study estimated the clinical effectiveness of five different antibiotic regimens (doxycycline, chloramphenicol, ciprofloxacin, doxycycline plus chloramphenicol, and doxycycline plus ciprofloxacin) administered for infection with Rickettsia typhi in terms of the duration of the fever. Eighty-seven patients with endemic typhus were hospitalized between 1993 and 1998 at the General Hospital of Chania in Chania, Crete, Greece. The mean time to defervescence was 2.9 days for doxycycline, 4.0 days for chloramphenicol, and 4.2 days for ciprofloxacin. In patients receiving combinations of doxycycline plus chloramphenicol and doxycycline plus ciprofloxacin, fever subsided in 3.4 and 4.0 days, respectively. The outcome was favorable in all patients, and no deaths or relapses were observed within two months.
A SINGLE MULTIPLEX ASSAY TO IDENTIFY MAJOR MALARIA VECTORS WITHIN THE AFRICAN ANOPHELES FUNESTUS AND THE ORIENTAL AN. MINIMUS GROUPS
Authors: GARROS CLAIRE , KOEKEMOER LIZETTE L. , COETZEE MAUREEN , COOSEMANS MARC , MANGUIN SYLVIE
Published: September 2018

The African Anopheles funestus and the Oriental An. minimus groups are closely related and composed of major malaria vectors in Africa and Southeast Asia, respectively. None of the species of either the An. funestus or the An. minimus group can be identified with absolute certainty using the adult morphology. Polymorphisms present on the internal transcribed spacer 2 (ITS2) of ribosomal DNA allowed the development of 10 primers that combined with an universal forward primer lead to a simple and sensitive multiplex allele-specific polymerase chain reaction (AS-PCR). Moreover, the possible additional amplification of the entire ITS2 allows one to detect other anopheline species in sympatry with members of both groups not included in this assay and serves as a control band. This universal PCR method permits the discrimination of 10 species within the subgenus Cellia, among which figure three major malaria vectors, and constitutes a very efficient and powerful tool to improve our knowledge on these species distribution and biology. Not only restricted to anophelines, this AS-PCR could also be developed and applied to other insect groups.
DYNAMICS OF THE PYRETHROID KNOCKDOWN RESISTANCE ALLELE IN WESTERN KENYAN POPULATIONS OF ANOPHELES GAMBIAE IN RESPONSE TO INSECTICIDE-TREATED BED NET TRIALS
Authors: STUMP ARAM D. , ATIELI FRANCIS K. , VULULE JOHN M. , BESANSKY NORA J.
Published: September 2018

Permethrin and DDT resistance in Anopheles gambiae s.s. associated with a leucine-serine knockdown resistance (kdr) mutation in the voltage-gated sodium channel gene was discovered recently in western Kenya where a large scale permethrin-impregnated bed net (ITN) program has been implemented. Collections of An. gambiae s.l. were made from intervention and control villages prior to and after onset of the program. The kdr genotypes were determined using allele-specific polymerase chain reaction diagnostic tests. In An. gambiae s.s., the frequency of the kdr mutation prior to ITN introduction was ~3–4% in western Kenya and zero in samples from the coast. After ITN introduction, the kdr mutation increased in ITN and neighboring villages from ~4% to ~8%, but remained unchanged in villages at least 20 km distant and was not detected in coastal Kenya. The identical leucine-serine mutation was found in a single An. arabiensis individual among 658 tested. The leucine-phenylalanine kdr mutation common in west African An. gambiae populations was not detected in An. gambiae s.l. from Kenya. Implications for the population structure and control of An. gambiae are discussed.
SHORT REPORT: A NEW POLYMERASE CHAIN REACTION-RESTRICTION FRAGMENT LENGTH POLYMORPHISM METHOD TO IDENTIFY ANOPHELES ARABIENSIS FROM AN. GAMBIAE AND ITS TWO MOLECULAR FORMS FROM DEGRADED DNA TEMPLATES OR MUSEUM SAMPLES
Authors: SANTOLAMAZZA FEDERICA , DELLA TORRE ALESSANDRA , CACCONE ADALGISA
Published: September 2018

We present a polymerase chain reaction-restriction fragment length polymorphism method to simultaneously distinguish the two Anopheles gambiae M and S molecular forms and Anopheles arabiensis. This method uses different diagnostic sites than previously published methods, and it is based on the amplification of a smaller ribosomal DNA fragment. We have tested this protocol in a variety of samples from different geographic regions and various ages of preservation to ascertain the robustness of this protocol over a wide geographic window and on DNA templates of poor quality. This procedure is as efficient as previous ones in discriminating An. arabiensis from the two taxa in An gambiae s.s. However, it performs better than others on poor quality templates such as the ones from museum collections, and poorly stored field collected material. However, it must be noted that it does not allow the simultaneous discrimination of all the species in the An. gambiae complex.
GENETIC POLYMORPHISM WITHIN THE LEISHMANIA DONOVANI COMPLEX: CORRELATION WITH GEOGRAPHIC ORIGIN
Authors: ZEMANOVÁ EVA , JIRKŮ MILAN , MAURICIO ISABEL L. , MILES MICHAEL A. , LUKEŠ JULIUS
Published: September 2018

Random amplified polymorphic DNA (RAPD) was used to detect intraspecific diversity for the Leishmania donovani complex. Fifty-two decameric to 21-meric primers of arbitrary sequence were applied to 15 strains that belong to nine zymodemes. Strains belonging to the species L. major and L. tropica were used as outgroups. A total of 902 amplicons generated by RAPD were scored. Most primers produced species-specific profiles, only 0.6% amplicons were shared by all species, while 4.3% amplicons were common for all 15 strains of the L. donovani complex. Well-supported trees have been constructed, which show a rather strong correlation between the genetic polymorphism of studied strains and their geographic origin. In all obtained trees, L. infantum was paraphyletic. The RAPD profiles suggest that MON-30 belongs to L. donovani. Moreover, the genetic distance between the L. archibaldi strain and other leishmanias does not warrant existence of a separate species.
ESTIMATING THE DURATION OF PLASMODIUM FALCIPARUM INFECTION FROM TRIALS OF INDOOR RESIDUAL SPRAYING
Authors: SAMA WILSON , KILLEEN GERRY , SMITH TOM
Published: September 2018

We reviewed the use of simple mathematical models to estimate the duration of Plasmodium falciparum infection after transmission has been interrupted. We then fit an exponential decay model to repeated cross-sectional survey data collected from three historical trials of indoor residual spraying against malaria: one from two contiguous districts in Tanzania-Kenya (Pare Taveta) carried out in 1954, the others in West Papua (1953), and the Garki project in northern Nigeria (1972–1973). A cross-sectional analysis of these datasets gave overall estimates of 602 days (95% confidence interval [CI] = 581–625) for the infection duration in Pare Taveta, 734 days (95% CI = 645–849) in West Papua, and 1,329 days (95% CI =1,193–1,499) for Garki. These estimates are much greater than the most widely quoted figures for the duration of untreated P. falciparum infections. Although these may be exaggerated because some reinfections occurred despite intensive vector control, prevalence was still decreasing when all these projects ended. Longitudinal survival analysis of the Garki data gave much shorter estimates of duration (186 days, 95% CI = 181–191), but effects of imperfect detection of parasites by microscopy severely bias these estimates. Estimates of infection duration for different age groups showed considerable variation but no general age trend. There was also no clear relationship between malaria endemicity and infection duration. Analyses of successive sampling from the same individuals with parasite typing are needed to obtain more reliable estimates of infection duration in endemic areas. Periods of several years may be required to evaluate long-term effects of interventions on malaria prevalence.
SHORT REPORT: HIGH PREVALENCE OF MULTIDRUG-RESISTANT PLASMODIUM FALCIPARUM MALARIA IN THE FRENCH TERRITORY OF MAYOTTE
Authors: PETTINELLI FRANÇOIS , PETTINELLI MARIE-EDITH , DE PÉCOULAS PHILIPPE ELDIN , MILLET JULIE , MICHEL DELPHINE , BRASSEUR PHILIPPE , DRUILHE PIERRE
Published: September 2018

A drug-resistance survey was conducted in the French territory of Mayotte in the Comorian Islands in the Indian Ocean where malaria is endemic. A high prevalence of resistant Plasmodium falciparum parasites was observed, not only to chloroquine (88%) and pyrimethamine (99%), but more surprisingly to quinine (17%), mefloquine (9%), and amodiaquine (24%). This leaves few treatment alternatives other than artemisine-mefloquine combinations. However, despite notification to French Health authorities three years ago, inadequate treatment (chloroquine plus sulfadoxine-pyrimethamine) is still used in this locality. Thus, people still die of malaria in this remote territory of France.
A RETROSPECTIVE EXAMINATION OF REINFECTION OF HUMANS WITH PLASMODIUM VIVAX
Authors: COLLINS WILLIAM E. , JEFFERY GEOFFREY M. , ROBERTS JACQUELIN M.
Published: September 2018

A retrospective examination was made of archival data collected between 1940 and 1963 to determine the impact of reinfection of patients with Plasmodium vivax with homologous and heterologous strains of the parasite. Following reinfection of 14 patients with a homologous strain, the geometric mean maximum parasite count was reduced from 9,101/μL during the primary infection to 998/μL and the geometric mean daily parasite count for the first 20 days was reduced from 923/μL to 16/μL. Following reinfection of 22 patients with heterologous strains of P. vivax, the geometric mean maximum parasite count was 8,460/μL during the primary infection versus a secondary level of 9,196/μL and the geometric mean daily parasite count decreased from 847/μL/day to 335/μL/day. Reductions in fever episodes ≥101°F and ≥ 104°F appeared to be a more sensitive measure of clinical immunity. Fever episodes ≥104°F in patients with homologous strain reinfections decreased from 1.92 episodes per week to 0.18 compared with 1.24 to 0.57 in patients with heterologous infections. Fever episodes ≥101°F decreased from 2.98 to 0.60 in the homologous strain compared with 2.08 to 1.07 for the heterologous infections. The average maximum fever temperature in the homologous group was 106°F during the primary infection versus 103.4°F for the secondary infection compared with 105.8°F during the primary infections versus 105.6°F for the secondary infection in the heterologous patients.
THE ETIOLOGY OF FEBRILE ILLNESS IN ADULTS PRESENTING TO PATAN HOSPITAL IN KATHMANDU, NEPAL
Authors: MURDOCH DAVID R. , WOODS CHRISTOPHER W. , ZIMMERMAN MARK D. , DULL PETER M. , BELBASE RAM HARI , KEENAN ANDREW J. , SCOTT ROBERT MCNAIR , BASNYAT BUDDHA , ARCHIBALD LENNOX K. , RELLER L. BARTH
Published: September 2018

In Nepal, many infections remain poorly characterized, partly due to limited diagnostic facilities. We studied consecutive febrile adults presenting to a general hospital in Kathmandu, Nepal. Of the 876 patients enrolled, enteric fever and pneumonia were the most common clinical diagnoses. Putative pathogens were identified in 323 (37%) patients, the most common being Salmonella enterica serotype Typhi and S. enterica serotype Paratyphi A (117), Rickettsia typhi (97), Streptococcus pneumoniae (53), Leptospira spp. (36), and Orientia tsutsugamushi (28). Approximately half of the Salmonella isolates were resistant to nalidixic acid. No clinical predictors were identified to reliably distinguish between the different infections. These findings confirm the heavy burden of enteric fever and pneumonia in Kathmandu, and highlight the importance of murine typhus, scrub typhus, and leptospirosis. Given the lack of reliable clinical predictors, the development of cheap and accurate diagnostic tests are likely to be of great clinical utility in this setting.
THE 2002 INTRODUCTION OF WEST NILE VIRUS INTO HARRIS COUNTY, TEXAS, AN AREA HISTORICALLY ENDEMIC FOR ST. LOUIS ENCEPHALITIS
Authors: LILLIBRIDGE KRISTY M. , PARSONS RAY , RANDLE YVONNE , TRAVASSOS DA ROSA AMELIA P. A. , GUZMAN HILDA , SIIRIN MARINA , WUITHIRANYAGOOL TAWEESAK , HAILEY CHRISTINA , HIGGS STEPHEN , BALA ADIL A. , PASCUA RHIA , MEYER TAMRA , VANLANDINGHAM DANA L. , TESH ROBERT B.
Published: September 2018

Harris County, Texas, is an endemic area of St. Louis encephalitis (SLE); and an active surveillance program that monitors SLE virus activity in mosquitoes, birds, and humans has been in place there for the past 28 years. In June of 2002, West Nile (WN) virus appeared in Houston and quickly spread throughout the region. This report describes the results of 12 years of SLE surveillance in Harris County and the contrasting pattern of WN virus activity, when it arrived in 2002. Our data indicate that both SLE and WN viruses can coexist, despite their ecologic, antigenic, and genetic similarities, and that both viruses will probably persist in this geographic region.
USE OF THE BRUCELLA IgM AND IgG FLOW ASSAYS IN THE SERODIAGNOSIS OF HUMAN BRUCELLOSIS IN AN AREA ENDEMIC FOR BRUCELLOSIS
Authors: IRMAK HASAN , BUZGAN TURAN , EVIRGEN ÖMER , AKDENIZ HAYRETTIN , DEMIROZ A. PEKCAN , ABDOEL THERESIA H. , SMITS HENK L.
Published: September 2018

The clinical utility of two complementary tests for brucellosis, the Brucella IgM and IgG flow assays, was evaluated in a hospital in eastern Turkey. The results show that the flow assays are convenient diagnostic tests for use in endemic areas. A positive result in the flow assays was obtained in 91% and 97% of the admission sera from adult and pediatric patients with brucellosis, respectively, and the sensitivity at admission was 100% for culture-confirmed brucellosis. The assay system performed equally well in diagnosing patients at different stages of illness including patients with acute, subacute, or chronic disease and with relapse. The results of the flow assays correlated well with those of a serum agglutination test at a cut-off ≥1:160. The agreement was 92%. Application of the flow assays on serum samples collected during a village survey for brucellosis after an outbreak demonstrated their diagnostic potential as field tests.
PREVALENCE OF INFECTION WITH WATERBORNE PATHOGENS: A SEROEPIDEMIOLOGIC STUDY IN CHILDREN 6–36 MONTHS OLD IN SAN JUAN SACATEPEQUEZ, GUATEMALA
Authors: STEINBERG ELLEN B. , MENDOZA CARLOS E. , GLASS ROGER , ARANA BYRON , LOPEZ M. BEATRIZ , MEJIA MARICRUZ , GOLD BENJAMIN D. , PRIEST JEFFREY W. , BIBB WILLIAM , MONROE STEPHAN S. , BERN CARYN , BELL BETH P. , HOEKSTRA ROBERT M. , KLEIN ROBERT , MINTZ ERIC D. , LUBY STEPHEN
Published: September 2018

Water and sanitation interventions in developing countries have historically been difficult to evaluate. We conducted a seroepidemiologic study with the following goals: 1) to determine the feasibility of using antibody markers as indicators of waterborne pathogen infection in the evaluation of water and sanitation intervention projects; 2) to characterize the epidemiology of waterborne diarrheal infections in rural Guatemala, and 3) to measure the age-specific prevalence of antibodies to waterborne pathogens. Between September and December 1999, all children 6–36 months of age in 10 study villages were invited to participate. We collected sufficient serum from 522 of 590 eligible children, and divided them into six-month age groups for analysis (6–12, 13–18, 19–24, 25–30, and 31–36 months). The prevalence of antibodies was lowest in children 6–12 months old compared with the four older age groups for the following pathogens: enterotoxigenic Escherichia coli (48%, 81%, 80%, 77%, and 83%), Norwalk virus (27%, 61%, 83%, 94%, and 94%), and Cryptosporidium parvum (27%, 53%, 70%, 67%, and 73%). The prevalence of total antibody to hepatitis A virus increased steadily in the three oldest age groups (40%, 28%, 46%, 60%, and 76%). In contrast, the prevalence of antibody to Helicobacter pylori was relatively constant in all five age groups (20%, 19%, 21%, 25%, and 25%). Serology appears to be an efficient and feasible approach for determining the prevalence of infection with selected waterborne pathogens in very young children. Such an approach may provide a suitable, sensitive, and economical alternative to the cumbersome stool collection methods that have previously been used for evaluation of water and sanitation projects.
THE BURDEN OF MALARIA EPIDEMICS AND COST-EFFECTIVENESS OF INTERVENTIONS IN EPIDEMIC SITUATIONS IN AFRICA
Authors: WORRALL EVE , RIETVELD AAFJE , DELACOLLETTE CHARLES
Published: September 2018

Attempts to quantify the epidemiologic and economic burden of malaria have so far neglected to specifically address the burden of epidemic malaria. Moreover, the data on the effectiveness and cost-effectiveness of interventions in epidemics is extremely limited. Answering such key questions in an epidemic prone context is more challenging than doing so in endemic areas. Using the limited data available, we estimate that in Africa, there are more than 12 million malaria episodes and 155,000–310,000 malaria deaths per year attributable to epidemics if control options are not implemented or well timed, which is equivalent to some 4% of estimated annual malaria cases worldwide and 12–25% of estimated annual worldwide malaria deaths, including up to 50% of the estimated annual worldwide malaria mortality in persons > 15 years of age. The possible economic impact of malaria epidemics is described and the limited evidence on the effectiveness and cost-effectiveness of interventions in areas of low or seasonal transmission is reviewed.
SEROPREVALENCE OF IgG SPECIFIC FOR DENGUE VIRUS AMONG ADULTS AND CHILDREN IN SANTO DOMINGO, DOMINICAN REPUBLIC
Authors: YAMASHIRO TETSU , DISLA MILDRE , PETIT ANGELA , TAVERAS DELFIS , CASTRO-BELLO MERCEDEZ , LORA-ORSTE MIGUEL , VARDEZ SONIA , CESIN ANA JULIA , GARCIA BARBARA , NISHIZONO AKIRA
Published: September 2018

The seroprevalence of dengue (DEN) virus-specific IgG was determined by enzyme-linked immunosorbent assay among 1,008 adults recruited at blood banks and among 201 children less than 10 years old visiting a hospital in Santo Domingo, Dominican Republic. Most (98%, 987 of 1,008) of the adults and 56% (113 of 201) of the children were positive for DEN virus-specific IgG. Among adults, there were no significant differences in the prevalence by age, sex, and residential area of the participants. Among children, the prevalence of DEN virus-specific IgG increased with age (1–2 years old, 0–5%; 3–6 years old, 25–65%; and ≥7 years old, 76–92%). The prevalence in 50% of those less than one year of age was probably due to maternal antibody transfer. Neutralization tests of adult samples indicate that DEN virus infections with different serotypes have occurred sequentially or simultaneously among the inhabitants of Santo Domingo.
THE SOCIAL BURDEN OF MALARIA: WHAT ARE WE MEASURING?
Authors: JONES CAROLINE O. H. , WILLIAMS HOLLY A.
Published: September 2018

Definitions of the burden of malaria vary by public health discipline. Epidemiologists and economists commonly use a quantitative approach to measure risk factors and associate them with disease outcomes. In contrast, since burden is itself a cultural construct, an anthropologic perspective of the burden of disease considers the sociocultural context in which these risk factors exist. This broader concept of burden is rarely tackled, most likely stemming from a lack of understanding of what is meant by the term social burden. This report describes the concept from an anthropologic perspective. The aim is to provide a better understanding of the process through which social and cultural factors affect the biomedical burden of malaria. The consequences of adopting this perspective for public health in general and malaria interventions in particular are discussed.
ARTESUNATE WITH MEFLOQUINE AT VARIOUS INTERVALS FOR NON-SEVERE PLASMODIUM FALCIPARUM MALARIA
Authors: HUNG LE Q. , DE VRIES PETER J. , BINH TRAN Q. , GIAO PHAN T. , NAM NGUYEN V. , HOLMAN R. , KAGER PIET A.
Published: September 2018

To study the efficacy, tolerance, population pharmacokinetics and pharmacodynamics of artesunate followed by mefloquine at various intervals, 360 patients with Plasmodium falciparum malaria received 4 mg/kg of artesunate and thereafter 15 mg/kg of mefloquine simultaneously (group A), after 8 hours (after group B), and after 24 hours (group C). Three dosages were completed with placebo. Follow-up was 28 days. All patients recovered rapidly except one case of failure within the first 24 hours. Mefloquine pharmacokinetics was similar in the three regimens. Parasites reappeared in 26%, 26%, and 33% of the patients in groups A, B, and C, respectively. Early recrudescence was associated with high initial parasite density, slow parasite clearance, and rapid mefloquine clearance and low plasma concentrations at day 28. Mefloquine plasma concentrations all reached therapeutic ranges, suggesting reduced parasite sensitivity. In conclusion, there is no interaction between artesunate and mefloquine with respect to tolerance, efficacy, and pharmacokinetics. Single-dose combination therapy with artemisinin drugs and 15 mg/kg of mefloquine does not completely prevent parasite recurrence and may not prevent mefloquine resistance.
DO MALARIA CONTROL INTERVENTIONS REACH THE POOR? A VIEW THROUGH THE EQUITY LENS
Authors: BARAT LAWRENCE M. , PALMER NATASHA , BASU SUPROTIK , WORRALL EVE , HANSON KARA , MILLS ANNE
Published: September 2018

Malaria, more than any other disease of major public health importance in developing countries, disproportionately affects poor people, with 58% of malaria cases occurring in the poorest 20% of the world’s population. If malaria control interventions are to achieve their desired impact, they must reach the poorest segments of the populations of developing countries. Unfortunately, a growing body of evidence from benefit-incidence analyses has demonstrated that many public health interventions that were designed to aid the poor are not reaching their intended target. For example, the poorest 20% of people in selected developing countries were as much as 2.5 times less likely to receive basic public health services as the least-poor 20%. In the field of malaria control, a small number of studies have begun to shed light on differences by wealth status of malaria burden and of access to treatment and prevention services. These early studies found no clear difference in fever incidence based on wealth status, but did show significant disparities in both the consequences of malaria and in the use of malaria prevention and treatment services. Further study is needed to elucidate the underlying factors that contribute to these disparities, and to examine possible inequities related to gender, social class, or other factors. To achieve impact and overcome such inequities, malaria control efforts must begin to incorporate approaches relevant to equity in program design, implementation, and monitoring and evaluation.
A THRESHOLD ANALYSIS OF THE COST-EFFECTIVENESS OF ARTEMISININ-BASED COMBINATION THERAPIES IN SUB-SAHARAN AFRICA
Authors: COLEMAN PAUL G. , MOREL CHANTAL , SHILLCUTT SAM , GOODMAN CATHERINE , MILLS ANNE J.
Published: September 2018

Artemisinin-based combination therapies (ACTs) are generally regarded as vital in addressing the growing problem posed by the development of antimalarial resistance across sub-Saharan Africa. However, the costs of the new ACTs are likely to be significantly higher than current therapies. Therefore, it is important to examine formally the cost-effectiveness of the more effective yet more expensive ACTs before advocating a switch in policy. Importantly, any such economic evaluation must consider the temporal dynamics of drug resistance, and not just focus on the static question of whether switching today would be cost-effective at current levels of resistance, particularly since the development of new antimalarials in the future is so uncertain. However, predicting the future changes in drug resistance is a major difficulty in accurately quantifying the relative costs and health outcomes associated with different drug therapies over time. Here, we use a simple decision tree model to estimate the incremental cost-effectiveness of using ACTs, compared with persisting with current therapies, over 5-, 10-, and 15-year periods. We describe the dynamics of drug resistance using a general logistic growth function, in which the starting frequency of resistance and maximum growth may be altered. However, rather than make assumptions about the absolute rate at which resistance to ACTs will progress, we allow the ratio of the growth rate of resistance to ACTs relative to that of current therapies to vary. Defining the growth rate of ACT resistance in this manner allows us to calculate the threshold ratio at which ACTs would no longer appear cost-effective, for any starting conditions of resistance to current therapies and ACTs, and over any time period. The influence of uncertainty in other decision tree parameters on the threshold ratio values is also quantified, using Monte Carlo simulation techniques. This analysis shows that ACTs are more than 95% likely to be cost-effective under most conditions, other than very low levels of initial resistance to sulfadoxine/pyrimethamine and a five-year time frame. These predictions are conservative in that 95% certainty is a stringent decision rule favoring the rejection of new policies. The importance of other variables not included in the analysis for the robustness of the findings are discussed (e.g., consideration of the entire population at risk for malaria, the affordability of ACTs in specific settings, and the growth of resistance modeled according to population genetic parameters).
SHORT REPORT: THE ACTIVITY OF PAMAQUINE, AN 8-AMINOQUINOLINE DRUG, AGAINST SPOROZOITE-INDUCED INFECTIONS OF PLASMODIUM VIVAX (NEW GUINEA STRAINS)
Authors: SWEENEY ANTHONY W. , BLACKBURN CHARLES R. B. , RIECKMANN KARL H.
Published: September 2018

It was reported in 1946 that the administration of pamaquine during the incubation period delayed but did not prevent primary attacks of a New Guinea strain of Plasmodium vivax malaria. The observation that none of the four test subjects in this study had relapses has not previously been published and may have important implications for the evaluation of other 8-aminoquinoline compounds against relapsing vivax malaria.
LACK OF EVIDENCE FOR AN ANTISCHISTOSOMAL ACTIVITY OF MYRRH IN EXPERIMENTAL ANIMALS
Authors: BOTROS SANAA , WILLIAM SAMIA , EBEID FATMA , CIOLI DONATO , KATZ NAFTALE , DAY TIM A. , BENNETT JAMES L.
Published: September 2018

In a multicenter investigation of the potential antischistosomal activity of myrrh, a resin obtained from an African plant, different derivatives of the resin, including the commercial preparation Mirazid, were tested at different doses in mice and hamsters infected with Schistosoma mansoni. In mice infected with the Egyptian (CD) strain of S. mansoni, four of six groups treated with Mirazid did not show significant worm reduction, while the remaining groups showed significant but trivial reductions. In mice infected with the Puerto Rican (Mill Hill) strain of S. mansoni, a Mirazid solution was toxic for mice at high doses and produced modest or no worm reduction at lower doses. In hamsters and mice infected with Puerto Rican (NMRI) and Brazilian (LE) strains of S. mansoni and treated with the crude extract of myrrh in doses ranging from 180 to 10,000 mg/kg, no signs of antibilharzial activity were observed. Total tissue egg load and egg developmental stages were not affected by any of the treatment regimens. These results were in contrast to those obtained in praziquantel-treated animals in which 94% worm reduction and 100% egg reduction was observed. Based on the findings of this work, we cannot recommend the use of Mirazid in human cases of schistosomiasis.
OUTBREAK OF EOSINOPHILIC MENINGITIS ASSOCIATED WITH DRINKING RAW VEGETABLE JUICE IN SOUTHERN TAIWAN
Authors: TSAI HUNG-CHIN , LEE SUSAN SHIN-JUNG , HUANG CHUN-KAI , YEN CHUAN-MIN , CHEN ENG-RIN , LIU YUNG-CHING
Published: September 2018

The most common cause of eosinophilic meningitis is the rat lungworm Angiostrongylus cantonensis a parasite that is endemic in the southeast Asian and Pacific regions. Outbreaks of eosinophilic meningitis associated with drinking raw vegetable juice are rarely reported, even in regions of endemic infection. We performed a cohort study among Taiwanese with eosinophilic meningitis who drank raw vegetable juice within three months of the onset of the outbreak. Clinical manifestations, laboratory examinations, and outcomes were prospectively followed. Five native Taiwanese met the case definition of eosinophilic meningitis. Specific antibodies to A. cantonensis were detected in the serum of five of the patients and in the cerebrospinal fluid (CSF) of four of the patients. Central nervous system manifestations included headache (n = 5 [100%]), Brudzinski’s sign/stiff neck (n = 5 [100%]), hyperesthesia/paresthesias (n = 5 [100%]), and cranial nerve palsy (n = 1 [20%]). Laboratory findings included peripheral (n = 5 [100%]) and CSF eosinophilia (n = 4 [80%]), transient increases in the white blood cell count (n = 1 [20%]), and in serum levels of creatine kinase (n = 1 [20%]). Meningeal enhancement, as well as high signal intensity, at the subcortical white matter on T2 weighted and fluid attenuated inversion recovery images were observed on magnetic resonance imaging in four patients. There were three episodes of relapse during treatment and all resolved with after a lumbar puncture and/or administration of steroids. At the 12-month follow up, all five patients had recovered without neurologic sequelae. Risk factors identification showed that consumption of raw vegetable juice was associated with illness (Pearson correlation test r = 0.867, P = 0.01). There was association between the presence of raw vegetable juice and CSF eosinophilia (Spearman’s correlation test r = 0.816, P = 0.004).
MONITORING FUTURE IMPACT ON MALARIA BURDEN IN SUB-SAHARAN AFRICA
Authors: DE SAVIGNY DON , BINKA FRED
Published: September 2018

Ambitious new goals for control of malaria have been set and significant additional resources for malaria control are being mobilized. Yet for many of the countries most severely burdened by malaria, both baseline data and reliable monitoring of key impact indicators is lacking. For such countries, it will be difficult to know when targets are met or whether to make mid-course corrections if progress is inadequate. The new investments in malaria control have triggered resurgence in demand for health information, both for performance-based resource allocation and for health impact. We argue here that some of these resources will need to be diverted to support more integrated information systems able to monitor change and guide approaches, not just for malaria, but also for other important health and poverty related interventions. This paper urges a re-thinking of the nature of management information systems and sources in resource poor settings. A pathway is suggested that helps situate monitoring and evaluation more strategically in a framework of other information management steps for longitudinal, iterative, evidence-based decision making. Health Information Systems of the future will need much greater coherence in the use of information from disparate sources and much greater influence on action.
GENETIC SUBSTRUCTURING WITHIN OESOPHAGOSTOMUM BIFURCUM (NEMATODA) FROM HUMAN AND NON-HUMAN PRIMATES FROM GHANA BASED ON RANDOM AMPLIFIED POLYMORPHIC DNA ANALYSIS
Authors: DE GRUIJTER JOHANNA M. , ZIEM JUVENTUS , VERWEIJ JACO J. , POLDERMAN ANTON M. , GASSER ROBIN B.
Published: September 2018

Random amplified polymorphic DNA (RAPD) was used to study genetic variation within Oesophagostomum bifurcum in Ghana. Four different decamer primers were used for the amplification of DNA from individual O. bifurcum adults (n = 41) from humans and non-human primates (including the Mona monkey, Patas monkey and Olive baboon) from different geographic regions. Analysis of the amplicons from all 41 nematodes by high resolution, denaturing polyacrylamide gel electrophoresis defined a total of 326 informative RAPD bands. Cluster analysis of the RAPD data (based on pairwise comparison of banding profiles) showed that O. bifurcum from humans was genetically distinct from O. bifurcum from the Mona and Patas monkeys, and from the Olive baboon. These findings clearly demonstrate the existence of population genetic substructuring within O. bifurcum from different primate hosts in Ghana, and raise interesting questions about host specificity, epidemiology (e.g., zoonotic transmission), and ecology of the different genotypes of O. bifurcum.
UPDATE ON THE CLINICAL DEVELOPMENT OF CANDIDATE MALARIA VACCINES
Authors: BALLOU W. RIPLEY , AREVALO-HERRERA MYRIAM , CARUCCI DANIEL , RICHIE THOMAS L. , CORRADIN GIAMPIETRO , DIGGS CARTER , DRUILHE PIERRE , GIERSING BIRGITTE K. , SAUL ALLAN , HEPPNER D. GRAY , KESTER KENT E. , LANAR DAVID E. , LYON JEFF , HILL ADRIAN V. S. , PAN WEIQING , COHEN JOE D.
Published: September 2018

The recent availability of significantly increased levels of funding for unmet medical needs in the developing world, made available by newly created public-private-partnerships, has proven to be a powerful driver for stimulating clinical development of candidate vaccines for malaria. This new way forward promises to greatly increase the likelihood of bringing a safe and effective vaccine to licensure. The investigators bring together important published and unpublished information that illuminates the status of malaria vaccine development. They focus their comments on those candidate vaccines that are currently in or expected to enter clinical trials in the next 12 months.
ARE MULTILATERAL MALARIA RESEARCH AND CONTROL PROGRAMS THE MOST SUCCESSFUL? LESSONS FROM THE PAST 100 YEARS IN AFRICA
Authors: ALILIO MARTIN S. , BYGBJERG IB C. , BREMAN JOEL G.
Published: September 2018

Multilateral malaria research and control programs in Africa have regained prominence recently as bilateral assistance has diminished. The transnational nature of the threat and the need for inspired leadership, good coordination, and new discoveries to decrease the impact of the disease has led to the founding of the Multilateral Initiative on Malaria, the Roll Back Malaria Project, Global Fund for HIV, Tuberculosis and Malaria (Global Fund), the Medicines for Malaria Venture, and the Malaria Vaccine Initiative, among other groups. Historically, the most striking feature of malaria control and elimination activities was the connectedness and balance between malaria research and control especially, from 1892 to 1949. A combination of scientific originality, perseverance in research, integrated approaches, and social concern were the keys for success. The elimination of Anopheles gambiae from Upper Egypt in 1942 using integrated vector control methods is a prime example of malaria control during the first half of the 20th century where those factors were brought together. After 1949, there were three decades of great optimism. Four notable landmarks characterized this period: the Kampala Conference in 1950; the Global Malaria Eradication Program beginning in 1955; the primary health care strategies adopted by most African States after attaining their political independence in the 1960s, and accelerating in the 1980s; and creation of the Special Program in Training and Research in Tropical Diseases at the World Health Organization in 1975. The initial highly encouraging operational results, largely obtained in temperate or subtropical areas where transmission was unstable, engendered undue expectations for the success of identical antimalarial measures elsewhere. Many were convinced that the eradication was in sight, such that support for malaria research virtually ceased. Young, bright scientists were discouraged from seeking a career in a discipline that appeared to soon become superfluous. It took more than three decades to modify antimalarial strategies and to rehabilitate long-term control as an intermediate objective. In Africa, although multilateral malaria programs have grown over the past half century and proved the most successful, fragmentation of co-ordination remains and is a major challenge. The proliferation of malaria programs in the late 1990s has brought substantial additional funds and expertise. However, excessive funding competition and failure of different programs to collaborate has resulted in poor communication and duplication of activities. The capacities of the African nations to conduct high-quality research and to coordinate control efforts are in great jeopardy. There is an urgent need for a non-partisan umbrella organ to coordinate and facilitate the network of alliances and programs in malaria research and control in Africa.
POLYMERASE CHAIN REACTION DIAGNOSIS AND THE CHANGING PATTERN OF VECTOR ECOLOGY AND MALARIA TRANSMISSION DYNAMICS IN PAPUA NEW GUINEA
Authors: BENET ARIADNA , MAI ABSALOM , BOCKARIE FLORENCE , LAGOG MOSES , ZIMMERMAN PETER , ALPERS MICHAEL P. , REEDER JOHN C. , BOCKARIE MOSES J.
Published: September 2018

The ecology and behavior of most of the 11 known members of the Anopheles punctulatus group remain unresolved and only the morphologic species An. farauti, An. koliensis, and An. punctulatus are known as vectors of malaria in Papua New Guinea. Of 1,582 mosquitoes examined morphologically, 737 were identified as An. farauti s.l., 719 as An. koliensis, and 126 as An. punctulatus. All specimens identified morphologically as An. punctulatus were shown to be An. punctulatus by polymerase chain reaction–restriction fragment length polymorphism analysis, but the An. farauti and An. koliensis morphotypes consisted of three or more species including An. farauti s.s., An. farauti No. 2, and An. farauti No. 4. The biting cycles and role in malaria transmission of some of these species are described here for the first time. We also show evidence that An. koliensis could be a sub-complex of two or more species. The epidemiologic implications of our findings are discussed.
GENETIC DIVERSITY IN THE MEROZOITE SURFACE PROTEIN 1 GENE OF PLASMODIUM FALCIPARUM IN DIFFERENT MALARIA-ENDEMIC LOCALITIES
Authors: RAJ DIPAK KUMAR , DAS BIBHU RANJAN , DASH A. P. , SUPAKAR PRAKASH C.
Published: September 2018

A number of stage-specific antigens have been characterized for vaccine development in Plasmodium falciparum malaria. The polymorphic merozoite surface protein 1 (MSP-1) of Plasmodium falciparum is a major asexual blood stage malaria vaccine candidate antigen. In the present study, we analyzed the impact of hyperendemic malaria transmission, mesoendemic malaria transmission, and multiple infection on allelic diversity. We have used a simple strategy of polymerase chain reaction amplification and slot-blot hybridization to analyze variable regions of block-2, block-4 and blocks 6–10 of the MSP-1 gene. The allelic types of isolates collected from regions of hyperendemic malaria transmission (RHEMT) and mesoendemic malaria transmission (RMEMT) were compared. In RHEMT, 20 of 24 possible gene types were found among 163 isolates and more than one allelic type was found in 82 (50.3%) of the isolates. Thirteen of 24 possible gene types were found among 125 isolates in RMEMT and 27 (21.6%) of them contained more than one allele type. Our results suggest for the first time that the allelic distribution or allelic diversity and chances of finding multi-strain parasites in isolates in an area vary with the rate of transmission. Analyses of isolates containing more than one strain of parasite suggest that allelic types are randomly distributed, no specific type of alleles predominately show multi-strain infection, and neither strain of the parasite affect the process of infection and development of another.
CROSS-IMMUNITY EXPERIMENTS BETWEEN DIFFERENT SPECIES OR STRAINS OF LEISHMANIA IN RHESUS MACAQUES (MACACA MULATTA)
Authors: PORROZZI RENATO , TEVA ANTONIO , AMARAL VERONICA F. , SANTOS DA COSTA MARCOS V. , GRIMALDI GABRIEL
Published: September 2018

This study evaluates cross-immunity in rhesus monkeys (Macaca mulatta) previously infected with one species of Leishmania and have had self-cured disease or were cured by antimony-based therapy upon development of full-blown disease. We found that a self-healing cutaneous leishmaniasis (CL) following experimental infection with Leishmania (Leishmania) major induces significant protection for L. (L.) amazonensis and L. (Viannia) guyanensis, and was dependent on time of re-challenge by L (L.) amazonensis after animals had recovered from primary lesions, but lacked protection against L. (V.) braziliensis. In contrast, monkeys that recovered from L. (V.) braziliensis CL or L. (L.) chagasi visceral leishmaniasis following chemotherapeutic intervention were protected by challenge with L. (V.) braziliensis and L (L.) amazonensis. These findings indicate the relative variability in protection after self-cure or drug-cured experimental leishmaniasis to challenge by heterologous leishmanial parasites. Further studying the immune response may provide information regarding relevant factors influencing cross-protective immunity.
RATIONALIZING HISTORICAL SUCCESSES OF MALARIA CONTROL IN AFRICA IN TERMS OF MOSQUITO RESOURCE AVAILABILTY MANAGEMENT
Authors: KILLEEN GERRY F. , SEYOUM AKLILU , KNOLS BART G. J.
Published: September 2018

Environmental management of mosquito resources is a promising approach with which to control malaria, but it has seen little application in Africa for more than half a century. Here we present a kinetic model of mosquito foraging for aquatic habitats and vertebrate hosts that allows estimation of malaria transmission intensity by defining the availability of these resources as the rate at which individual mosquitoes encounter and use them. The model captures historically observed responses of malaria transmission to environmental change, highlights important gaps in current understanding of vector ecology, and suggests convenient solutions. Resource availability is an intuitive concept that provides an adaptable framework for models of mosquito population dynamics, gene flow, and pathogen transmission that can be conveniently parameterized with direct field measurements. Furthermore, the model presented predicts that drastic reductions of malaria transmission are possible with environmental management and elucidates an ecologic basis for previous successes of integrated malaria control in Africa before the advent of DDT or chloroquine. Environmental management for malaria control requires specialist skills that are currently lacking in sub-Saharan Africa where they are needed most. Infrastructure and human capacity building in clinical, public health, and environmental disciplines should therefore be prioritized so that growing financial support for tackling malaria can be translated into truly integrated control programs.