Papers by Patricia M Graves
American Journal of Tropical Medicine and Hygiene, Mar 1, 1989
The degree to which Anopheles punctulatus complex members feed on humans in different Papua New G... more The degree to which Anopheles punctulatus complex members feed on humans in different Papua New Guinea villages has a significant effect on sporozoite rates. Among villages, the human blood index (HBI) of the members of the complex varied with the average number of persons sharing a bednet. Although dogs are the preferred hosts by the 3 malaria vector species, the number of dogs did not significantly affect the HBI. The HBI was dependent upon the human-biting rate, implying increased avoidance of anophelines by people relative to other hosts at times of greater mosquito numbers. Human-biting rates and HBIs were also influenced by the distribution of alternative hosts relative to people.
Tropical Medicine and Infectious Disease, Apr 11, 2017
Diagnostic testing of blood samples for parasite antigen Og4C3 is used to assess Wuchereria bancr... more Diagnostic testing of blood samples for parasite antigen Og4C3 is used to assess Wuchereria bancrofti in endemic populations. However, the Tropbio ELISA recommends that plasma and dried blood spots (DBS) prepared using filter paper be used at different dilutions, making it uncertain whether these two methods and dilutions give similar results, especially at low levels of residual infection or resurgence during the post-program phase. We compared results obtained using samples of plasma and DBS taken simultaneously from 104 young adults in Myanmar in 2014, of whom 50 (48.1%) were positive for filariasis antigen by rapid antigen test. Results from DBS tests at recommended dilution were significantly lower than results from plasma tested at recommended dilution, with comparisons between plasma and DBS at unmatched dilutions yielding low sensitivity and negative predictive values of 60.0% and 70.6% respectively. While collection of capillary blood on DBS is cheaper and easier to perform than collecting plasma or serum, and does not need to be stored frozen, dilutions between different versions of the test must be reconciled or an adjustment factor applied.
National Academies Press eBooks, 2006
Malaria is an infectious disease common to several parts of the world, including Africa, northern... more Malaria is an infectious disease common to several parts of the world, including Africa, northern South America, and Asia. During their service in the military, U.S. active members may be sent to any part of the world, including parts of the world where Malaria is an issue. In Liberia in 2003, for example, there was a 28 percent attack rate in Marines who spent a short time ashore, and half of the 80 Marines affected needed to be evacuated to Germany. This was not only costly to the U.S. military but dangerous as well. To fight against this disease, there exists a Malaria Vaccine program in the U.S. military. However, there exists a variety of potential vaccine targets for the most severe and important form of malaria; malaria from the species Plasmodium falciparum. Issues also arise with the fact that there are three possible stages to create vaccines against-preerythrocytic, blood, or transmission. The Department of Defense (DoD), through the commanding general of the U.S. Army Medical Research and Materiel Command (USAMRMC), requested that the Institute of Medicine (IOM) conduct a programmatic review of the military Plasmodium falciparum malaria vaccine research and development program. There was to be a focus on vaccine against the preerythrocytic and blood stages. The IOM formed a committee of 11 experts with collective expertise in malaria vaccine research, parasite immunology, malarial biology, clinical trials and regulatory affairs, industrial and public-sector vaccine development, biologic products research and development (vaccinology), military research and development programs, tropical medicine, and public health. The committee focused different tasks including determining whether the DoD malaria vaccine research and development program is scientifically sound and able to achieve the vaccine program objectives within specified timelines, recommending how to overcome significant, identified barriers, and identifying major strategic goals and timelines based on the material received and presentations made by the DoD's program representatives. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program presents the committee's findings, current malaria vaccines, and recommendations for the development of the U.S. Military vaccine research.
medRxiv (Cold Spring Harbor Laboratory), Apr 11, 2020
The Cochrane library, Aug 19, 2020
PubMed, Apr 1, 1988
The prospects are reviewed of replacement of malaria vector populations by harmless mosquito popu... more The prospects are reviewed of replacement of malaria vector populations by harmless mosquito populations by means of: (i) ecologically competitive non-vector species; (ii) natural selection due to the harmfulness of being infected; (iii) selection for insecticide resistance genes; (iv) meiotic drive; (v) negative heterosis; and (vi) hybrid dysgenesis. Serious difficulties exist with all of these approaches. At present 'dilution', i.e. release of insects carrying the desired genes without any system for forcing population replacement is the only available method. It avoids the disadvantage that, in constructing elaborate genetic 'packages', factors for low fitness may be irreversibly incorporated into them. It is debatable whether release of males only or both sexes should be attempted.
American Journal of Tropical Medicine and Hygiene, Oct 1, 1990
Anopheline survivorship, vectorial capacity, and mosquito infection probability estimates from mo... more Anopheline survivorship, vectorial capacity, and mosquito infection probability estimates from mosquito infection rates were determined 4 times in 1 year in a Papua New Guinea village. Estimates of survivorship over the length of the extrinsic incubation period differed significantly during the year. However, survivorship per feeding cycle, individual mosquito vectorial capacity, and mosquito infection probability did not vary significantly. Estimates of these parameters were then compared to estimates of survivorship, individual vectorial capacity, and mosquito infection probability in mosquito populations in other villages in the study area. Since survivorship per feeding cycle did not vary significantly among the mosquito populations in these villages, changes in malaria transmission potential can be better gauged from estimates of survivorship over the length of the extrinsic incubation period. However, as measurements of relative inoculation rates are easier to perform and have been related to parasite prevalences in children in this area, estimates of inoculation rates are a preferred option for estimating malaria transmission in the Madang area of Papua New Guinea.
American Journal of Tropical Medicine and Hygiene, Jul 1, 1984
An immunoradiometric assay (IRMA) using a monoclonal antibody to the major surface protein of Pla... more An immunoradiometric assay (IRMA) using a monoclonal antibody to the major surface protein of Plasmodium falciparum sporozoites was used to assess the P. falciparum sporozoite rate in a West African population of Anopheles gambiae (s.1.). Unlike current dissection techniques, the IRMA could detect sporozoite antigen in dried as well as fresh mosquitoes. In a controlled comparison, the sensitivity of the IRMA was comparable that of the dissection technique. Additionally, the IRMA was species specific and quantitative. Sensitivity of the assay was sufficient to detect sporozoite infections resulting from the development of a single oocyst.
Tropical Medicine and Infectious Disease, Feb 10, 2017
Papua New Guinea (PNG) has a significant malaria burden, is resource constrained, and has isolate... more Papua New Guinea (PNG) has a significant malaria burden, is resource constrained, and has isolated populations with limited access to health services. Home-based management is a key element of the national program that supports strategies of early detection, diagnosis and treatment. We describe the epidemiology of malaria near Lake Kutubu in the Southern Highlands Province through reported data on suspected and confirmed malaria in patients accessing public health facilities or using a novel, incentivised, social marketing approach for malaria treatment at the village level. Monthly case data reported by nine health facilities and 14 village-based providers, known as Marasin Stoa Kipas (MSK), were extracted from outpatient registers and MSK malaria case forms. Descriptive statistics of diagnostic use, monthly incidence, test positivity rate and species distribution were estimated. Summary statistics of service delivery demonstrate patient access and diagnostic coverage in program areas. From May 2005 to September 2013, 15,726 individuals were tested with either rapid diagnostic test and/or microscopy at health facilities, and 42% had a positive result for malaria (n = 6604); of these 67.1% (n = 4431) were positive for P. falciparum (alone or mixed) and 32.9% were positive for non-P. falciparum species (alone or mixed). From October 2007 to September 2013, 9687 individuals were tested with either RDT and/or microscopy at MSK sites and 44.2% (n = 4283) tested positive for malaria; of these, 65.3% (n = 2796) were positive for P. falciparum, while 34.7% (n = 1487) were positive for non-P. falciparum species. Up to April 2010 there was an intermittent and upward trend in the reported incidence of all species of confirmed malaria, reaching 50 per 1000 population per month for both sites combined, followed by a steady decline to four per 1000 population per month in 2013, with P. vivax the most common infection. This study is the most recent longitudinal overview of malaria in the Southern Highlands since 2003. It outlines patient access to a community-based model of care. The analysis shows changes in health facility versus MSK use, a strongly decreasing trend in incidence of confirmed malaria from 2010 to 2013, and a shift from predominantly P. falciparum to P. vivax infection.
Journal of Immunology, Oct 1, 1985
Leprosy Review, Sep 1, 2016
Leprosy is a Neglected Tropical Disease (NTD) causing significant physical and functional disabil... more Leprosy is a Neglected Tropical Disease (NTD) causing significant physical and functional disabilities around the world. The objective of this systematic review was to evaluate school-based leprosy screening as a means of identifying early leprosy cases. Using a structured search method, 30 suitable publications were identified. Whilst all studies included in this review were found to identify cases of leprosy through school-based screening, sample sizes were high and numbers detected were small, raising concerns about the feasibility and sustainability of school-based screening as a stand-alone intervention for leprosy detection. For school-based screening programmes to become a sustainable intervention, the inclusion of both capacity building and health education components into school-based screening and intervention programmes should be further explored. More research is needed to consider alternate methods which maximise the efficiency of school-based approaches in the early case detection of leprosy. Also, cases found at school may be used to find further active cases via family and friends. School-based screening could be an effective solution for the early identification of leprosy particularly in areas of high endemicity, however to date there is limited data on its effectiveness compared with other interventions.
medRxiv (Cold Spring Harbor Laboratory), Mar 27, 2024
Background: Accurate and user-friendly rapid diagnostic tests (RDT) are needed to assess prevalen... more Background: Accurate and user-friendly rapid diagnostic tests (RDT) are needed to assess prevalence of Wuchereria bancrofti antigen in the Global Programme to Eliminate Lymphatic Filariasis (GPELF). We evaluated performance under laboratory conditions of the new Q Filariasis Antigen Test (QFAT) against the Filariasis Test Strip (FTS) for detecting antigen of Wuchereria bancrofti, a causative agent of lymphatic filariasis (LF). Methodology/Principal Findings: We compared test performance using available panels of serum (n=195) and plasma (n=189) from LF endemic areas in the Asia-Pacific region (Samoa, American Samoa and Myanmar) together with Australian negative controls (n=46). Prior antigen and antibody positivity status of endemic samples had been determined by rapid test or ELISA. The proportion of all samples testing positive at 10 minutes was higher with QFAT (44.8%) than FTS (41.3%). Concordance between tests was 93.5% (kappa 0.87, N=417) at 10 minutes, and increased over time to 98.8% (kappa 0.98) at 24 hours. Sensitivity of QFAT and FTS at 10 minutes compared to prior antigen results were 92% (95% CI 88.0-96.0) and 86% (95% CI 80.0-90.0), respectively. Specificity was 98% for QFAT and 99% for FTS at 10 minutes. Sensitivity increased over time for both tests, rising to 99% for QFAT and 97% for FTS at 24 hours. QFAT positively identified all microfilaria (Mf)-positive samples, whereas FTS was negative for 3 of 66 Mf-positives. For both QFAT and FTS, there was evidence of cross-reaction with Dirofilaria repens and Onchocerca lupi but not with Acanthochilonema reconditum, Cercopithifilaria bainae or Strongyloides. Disadvantages noted for QFAT were inconvenient packaging and an additional buffer step. Advantages of QFAT include easeof-use, smaller sample (10-20 µL vs 75 µL for FTS), clearer control line, and higher sensitivity for Mfpositive samples. Conclusions/Significance. Under lab conditions, QFAT is a suitable rapid Ag test for use in filariasis elimination programmes and has advantages over FTS.
Parasites & Vectors, Jan 11, 2013
Background: Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalenc... more Background: Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalence in some parts of Papua New Guinea. However, there has been no rigorous data-based representative assessment of nationwide prevalence of LF. The LF programme has been daunted by the scope of the problem, and progress on mass drug administration (MDA) has been slow and lacking in resources. Methods: A systematic literature review identified LF surveys in Papua New Guinea between 1980 and 2011. Results were extracted by location, time period and test used (blood slide, immunochromatographic test (ICT) or Og4C3 ELISA) and combined by district. Three criteria schemes based on the Global Programme to Eliminate Lymphatic Filariasis guidelines, with modifications, were developed to classify and prioritize districts by prevalence level. Results of repeated surveys in the same sites were used to investigate the impact of MDA on LF prevalence over the time period. Results: There were 312 distinct survey sites identified in 80 of the 89 districts over the 31-year period. The overall LF prevalence in the sites tested was estimated at 18.5 to 27.5% by blood slide for microfilariae (Mf), 10.1% to 12.9% by ICT and 45.4% to 48.8% by Og4C3. Biases in site selection towards areas with LF, and change in type of assay used, affected the prevalence estimates, but overall decline in prevalence over the time period was observed. Depending on the criteria used, 34 to 36 districts (population 2.7 to 2.9 million) were classed as high endemic (≥5% prevalence), 15 to 25 districts (1.7 to 1.9 million) as low endemic (<5%) and 20 to 31 (1.3 to 2.2 million) as nonendemic. Nine districts (0.7 million) had no information. The strong impact of MDA, especially on microfilaria (Mf) prevalence, was noted in sites with repeat surveys. Conclusions: This analytical review of past surveys of LF in Papua New Guinea enables better estimation of the national burden, identifies gaps in knowledge, quantifies and locates the population at risk, and can be used to predict the likely impact of MDA and/or vector control. Better targeting of districts by level of prevalence will strengthen the control programme, facilitate monitoring of the disease trend and increase the likelihood of reaching the target of LF elimination by 2020.
Archives of pediatrics & adolescent medicine, Oct 1, 1996
To investigate the association between maternal age and other risk factors and infant injury deat... more To investigate the association between maternal age and other risk factors and infant injury deaths in the state of Colorado from 1986 to 1992. A retrospective cohort design was used to compare rates of unintentional and intentional infant injury mortality by maternal age group. A case-control design explored the importance of various risk factors, particularly maternal age, using multivariate logistic regression. The 2 case groups comprised all unintentional and intentional injury deaths in the first year of life. The control group was a random sample of both survivors and noninjury deaths selected from the entire birth cohort. The infant injury mortality rate for the 322766 live births in Colorado from 1986 to 1992 was 3.1 per 10000. Intentional injury death rates were highest for infants of teenaged mothers, peaking at 10.5 per 10000 live births for mothers aged 16 years. Unintentional injury death rates were highest for infants of mothers aged 20 to 24 years, peaking at 3.7 per 10000 live births for 22-year-old mothers. For intentional injury death, maternal marital status had a significant impact on maternal age; compared with the baseline group of married mothers older than 24 years, significantly higher risks were observed for infants of teenagers who were married (odds ratio [OR] = 32.0; 95% confidence interval[CI], 9.9-104.0) but also in infants of older mothers who were unmarried (OR = 3.6; 95% CI, 1.0-13.0 for unmarried mothers aged 20-24 years and (OR = 7.7; 95% CI, 2.4-25.0 for those &gt; 24 years). Black race (OR = 3.5; 95% CI, 1.4-9.4) was also associated with intentional injury death. For unintentional injury death, the highest risk was for infants of mothers aged 20 to 24 years and unmarried (OR = 3.9; 95% CI, 1.7-9.3). Risk was also elevated for infants of married teenaged mothers (OR = 3.5; 95% CI, 0.7-17.8) but was not significantly different from the baseline group for unmarried teenagers, married 20- to 24-year-old mothers, or unmarried mothers aged 25 years or older. Risk was increased by the presence of older siblings (OR = 1.5 per sibling; 95% CI, 1.2-2.0). Maternal age and marital status significantly affect the rate of both unintentional and intentional infant injury mortality. These results suggest that child abuse prevention strategies should be targeted to teenaged mothers, and that strategies designed to prevent unintentional injuries should focus particularly on parents or caretakers of infants born to unmarried mothers in their early 20s as well as married teenagers.
Research Square (Research Square), Aug 18, 2020
Springer eBooks, 2004
... of Research);(c) oocyst on the mosquito gutnote blood in mosquito gut from a previous bloodm... more ... of Research);(c) oocyst on the mosquito gutnote blood in mosquito gut from a previous bloodmeal (photograph by Patricia M. Graves ... Cattani et al.(1986) de-scribed the importance of small area variations in malaria endemicity where consistent differ-ences in prevalence of ...
PLOS Neglected Tropical Diseases, Jun 8, 2016
Advances in disease vector research, 1994
The human malaria parasite life cycle appears deceptively simple because it involves only one spe... more The human malaria parasite life cycle appears deceptively simple because it involves only one species of vertebrate host (humans) and anopheline mosquitoes to transmit the pathogen. However, a number of host, vector, and pathogen factors have evolved that interact with ecological and logistic considerations to determine whether transmission of the parasite from a mosquito to a human, or the converse, will successfully occur.
Tropical Medicine and Health, 2007
Background Samoa was formerly highly endemic for Wuchereria bancrofti filariasis transmitted by A... more Background Samoa was formerly highly endemic for Wuchereria bancrofti filariasis transmitted by Aedes mosquitoes. Previous control efforts including sporadic mass drug administration (MDA) campaigns have reduced the prevalence to low levels but have not succeeded in eliminating the disease. To effectively plan, model and evaluate the worldwide elimination effort, the Global Programme to Eliminate Lymphatic Filariasis (GPFLF) needs data on filariasis epidemiology (including age and sex-specific prevalence and the density of microfilariae (Mf)) and estimates of the number of years of MDA required for elimination. The five-year nationwide MDA campaign carried out in Samoa before the start of the Pacific Programme to Eliminate Lymphatic Filariasis (PacELF) generated extensive data on these issues. Methodology/Principal Findings MDA campaigns were conducted in Samoa with diethylcarbamazine (DEC) in 1993 to 1995 and DEC plus ivermectin in 1996 to 1997 for all persons aged 2 years and above. Coverage of the MDA, as assessed from the campaign village register books, ranged from 62% to 97% depending on the year, and was over 80% in three out of five years. Village based surveys showed that prevalence of Mf declined from 4.3% in 1993 (N=10,256) to 1.1% in 1998 (N=4,054) (Pχ =94.4, p<0.001). Males had a three-to five-fold higher prevalence than females, and this difference remained consistent over the five-year period. Transmission was still occurring over the period as shown by the occurrence of new infections in 3 children less than 5 years old out of 5,691 tested (five-year cumulative incidence of 0.53 per thousand children for the period 1993 to 1998). There was a statistically significant reduction in the geometric mean number of Mf per 60 µl in positive cases between 1993 (11.8) and 1998 (6.9) (t=2.61; p<0.01). The proportion of people with a high density of Mf-over 60 Mf per 60 µl (1000 per ml)-declined from to 19.4% to 4.0% (Pχ =5.6, p=0.018). Conclusions/Significance Five years of sustained MDA with DEC (3 years) and DEC plus ivermectin (2 years) reduced the prevalence of Mf of W.bancrofti in Samoa by 74%. Density of Mf in infected individuals was also significantly reduced. Males had a three to five-fold higher prevalence than women. New infections in children less than five years old still occurred at a low level, suggesting that transmission was not completely interrupted. These findings helped to prepare a sound monitoring and evaluation plan for PacELF.
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Papers by Patricia M Graves