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Showing papers in "American Journal of Tropical Medicine and Hygiene in 2012"


Journal ArticleDOI
TL;DR: This work assessed correlation of volume of cholera-related HealthMap news media reports, Twitter postings, and governmentCholera cases reported in the first 100 days of the 2010 Haitian cholERA outbreak to find trends in volume of informal sources significantly correlated in time with official case data and was available up to 2 weeks earlier.
Abstract: During infectious disease outbreaks, data collected through health institutions and official reporting structures may not be available for weeks, hindering early epidemiologic assessment. By contrast, data from informal media are typically available in near real-time and could provide earlier estimates of epidemic dynamics. We assessed correlation of volume of cholera-related HealthMap news media reports, Twitter postings, and government cholera cases reported in the first 100 days of the 2010 Haitian cholera outbreak. Trends in volume of informal sources significantly correlated in time with official case data and was available up to 2 weeks earlier. Estimates of the reproductive number ranged from 1.54 to 6.89 (informal sources) and 1.27 to 3.72 (official sources) during the initial outbreak growth period, and 1.04 to 1.51 (informal) and 1.06 to 1.73 (official) when Hurricane Tomas afflicted Haiti. Informal data can be used complementarily with official data in an outbreak setting to get timely estimates of disease dynamics.

415 citations


Journal ArticleDOI
TL;DR: In this article, Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization (PAHO) are described, and the outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in theAmericas (1600-1946); Continental plan for the eradication of the Ae. aegypti (1947-1970) marked by a successful eradication in 18 continental countries by 1962; Ae.aegyptI reinfestation (1971-1999) caused by the failure of the mosquito eradication program; increased
Abstract: . Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600–1946); Continental plan for the eradication of the Ae. aegypti (1947–1970) marked by a successful eradication of the mosquito in 18 continental countries by 1962; Ae. aegypti reinfestation (1971–1999) caused by the failure of the mosquito eradication program; Increased dispersion of Ae. aegypti and dengue virus circulation (2000–2010) characterized by a marked increase in the number of outbreaks. During 2010 > 1.7 million dengue cases were reported, with 50,235 severe cases and 1,185 deaths. A dramatic increase in the number of outbreaks has been reported in recent years. Urgent global action is needed to avoid further disease spread.

345 citations


Journal ArticleDOI
TL;DR: The results show that parasites that fail to produce HRP2 can cause patent bloodstream infections and false-negative RDT results, and suggest that the use ofHRP2-based RDTs should be reconsidered.
Abstract: We identified 480 persons with positive thick smears for asexual Plasmodium falciparum parasites, of whom 454 had positive rapid diagnostic tests (RDTs) for the histidine-rich protein 2 (HRP2) product of the hrp2 gene and 26 had negative tests. Polymerase chain reaction (PCR) amplification for the histidine-rich repeat region of that gene was negative in one-half (10/22) of false-negative specimens available, consistent with spontaneous deletion. False-negative RDTs were found only in persons with asymptomatic infections, and multiplicities of infection (MOIs) were lower in persons with false-negative RDTs (both P < 0.001). These results show that parasites that fail to produce HRP2 can cause patent bloodstream infections and false-negative RDT results. The importance of these observations is likely to increase as malaria control improves, because lower MOIs are associated with false-negative RDTs and false-negative RDTs are more frequent in persons with asymptomatic infections. These findings suggest that the use of HRP2-based RDTs should be reconsidered.

264 citations


Journal ArticleDOI
TL;DR: The interacting effects of infection and enteropathy drive a vicious cycle that can propagate severe acute malnutrition, which underlies almost half of under-5-y deaths, and interventions to prevent or ameliorate enteropathies have potential to improve the health of millions of people in developing countries.
Abstract: A spectrum of enteropathies, characterized by small intestinal inflammation, reduced absorptive capacity, and increased intestinal permeability, commonly affect people in developing countries. This subclinical intestinal pathology facilitates microbial translocation across the compromised intestinal barrier, leading to chronic systemic inflammation that may adversely impact health. Environmental enteropathy (EE), ubiquitous among people living in unhygienic conditions, likely mediates two interlinked public health problems of childhood, stunting and anemia, and underlies poor oral vaccine efficacy in developing countries. Human immunodeficiency virus (HIV) enteropathy, which frequently overlaps with EE, may contribute to immune activation and modulate HIV disease progression. The interacting effects of infection and enteropathy drive a vicious cycle that can propagate severe acute malnutrition, which underlies almost half of under-5-y deaths. Enteropathies are therefore highly prevalent, interacting causes of morbidity and mortality in developing countries. Interventions to prevent or ameliorate enteropathies have potential to improve the health of millions of people in developing countries.

240 citations


Journal ArticleDOI
TL;DR: Dengue is the most important vector-borne viral disease of humans and likely more important than malaria globally in terms of morbidity and economic impact, and this study is the first study to show the societal distribution of the economic cost of dengue.
Abstract: Historically, dengue has been considered an unimportant public health problem because mortality rates were low and epidemics occurred only infrequently In the years after World War II, great progress was made in controlling infectious diseases of all kinds, especially vector-borne diseases, and the war on infectious disease was declared won in the late 1960s1 Coincident with this success in disease control was the economic recovery in some countries of Southeast Asia, and urban growth increased as people from rural areas migrated to the cities to find work The lack of planning, inadequate housing, water, sewage, and waste management in these cities created ideal conditions for dengue viruses and their mosquito vector Aedes aegypti, both of which had been spread widely in the region during World War II, to thrive2 The result was the emergence of epidemic dengue hemorrhagic fever During the 1950s and 1960s, the disease was limited to a few countries in Southeast Asia, but as economic growth expanded, the cities and epidemic dengue also grew, because little effort was made to control the mosquito vector In the 1970s and accelerating in the last two decades of the 20th century, epidemic dengue expanded regionally and globally Epidemics increased in both frequency and magnitude, and the viruses became hyperendemic (cocirculation of multiple virus serotypes) in most major cities of the tropics Despite this alarming emergence of a severe and fatal form of epidemic dengue, the disease was still considered a minor public health problem by policymakers In 2012, dengue is the most important vector-borne viral disease of humans and likely more important than malaria globally in terms of morbidity and economic impact The latest studies estimate 36 billion people living in areas of risk, over 230 million infections, millions of cases of dengue fever, over 2 million cases of the severe disease, and 21,000 deaths3 In addition to the public health and economic costs, there is a major social impact in those countries where large epidemics occur, often disrupting primary care for hospitalized patients4 Given the dramatic urban growth and lack of adequate surveillance for dengue in tropical developing countries in the past 50 years, it is likely that even these figures underestimate the true disease burden of dengue Thus, ignored for many years, only recently has the potential magnitude of the dengue problem been acknowledged by policymakers and funding agencies This acknowledgment has resulted in excellent progress in understanding dengue virus biology and development of dengue vaccines and antiviral drugs but not economic impact of the disease As the pipeline of dengue vaccine candidates, a number of which are already in clinical trials, has grown, it has become apparent that vaccine access will require more and better studies on the actual cost of dengue to endemic communities In recent years, many studies have been conducted in different Asian and American countries in attempts to measure the economic impact of dengue on a community Although most have contributed valuable information on the subject, none has provided comprehensive data on the actual cost of dengue disease The work by Halasa and others5 provides one of the best studies to date on that subject Working in collaboration with the Puerto Rico Department of Health and the US Centers for Disease Control and Prevention Dengue Branch in Puerto Rico, the investigators conducted a comprehensive review of 100 laboratory-confirmed dengue patients who experienced the disease between July of 2008 and March of 2010 The study included both adults and children and hospitalized and ambulatory care patients Records were reviewed for each patient, who was then subjected to a comprehensive interview about their illness and how it impacted their activities The work by Halasa and others5 measured the cost, both direct and indirect, of dengue in six categories of cases and went to considerable effort to validate their data The results, perhaps not surprisingly, show the economic burden of dengue in Puerto Rico to be very high This study is the first study to show the societal distribution of the economic cost of dengue, with the individual household bearing the largest burden (48%) compared with only 24% by the government and 22% by insurance5 The total annual cost of dengue between 2002 and 2010 was $4645 million ($418 million during the 9-year period)5 Clearly, there is a need to conduct more comprehensive studies of this kind in other dengue-endemic countries of the world These kinds of data are needed to allow policymakers and public health officials to make informed decisions on the cost efficacy of dengue control programs The private sector also needs comprehensive economic analyses to guide decision-making in vaccines and antiviral drug development Finally, international funding agencies require these kinds of data to establish priorities in public health funding Studies of this kind will always have limitations, and this study was no exception However, the work by Halasa and others5 clearly identified the most important limitations, such as recall bias and not being able to estimate the cost of tourism and deaths associated with dengue The latter two limitations, however, would add to the overall cost of dengue, driving the cost even higher The fact that the study was supported by a private vaccine manufacturer might raise questions about conflict of interest by some people In my mind, however, this possibility is not an issue because of the detailed methodology used and the reputation of the Brandeis group as the leader in research on the economic impact of dengue

240 citations


Journal ArticleDOI
TL;DR: The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States, based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgorferi.
Abstract: The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States. The map is based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgdorferi, which is closely associated with human infection risk. Risk factors for the presence and density of infected nymphs were used to model ac ontinuous 8k m+8 km resolution predictive surface of human risk, including confidence intervals for each pixel. Discontinuous Lyme disease risk foci were identified in the Northeast and upper Midwest, with a transitional zone includ- ing sites with uninfected I. scapularis populations. Given frequent under- and over-diagnoses of Lyme disease, this map could act as a tool to guide surveillance, control, and prevention efforts and act as a baseline for studies tracking the spread of infection.

231 citations


Journal ArticleDOI
TL;DR: This statement presents the latest evidence for integrated community case management of childhood illness, describes the necessary program elements and support tools for effective implementation, and lays out actions that countries and partners can take to support the implementation of integratedcommunity case management at scale.
Abstract: This statement presents the latest evidence for integrated community case management of childhood illness, describes the necessary program elements and support tools for effective implementation, and lays out actions that countries and partners can take to support the implementation of integrated community case management at scale.

230 citations


Journal ArticleDOI
TL;DR: A review summarizes novel findings and perspectives on artemisinin resistance, approaches for translating research data into relevant public health information, and opportunities for interdisciplinary collaboration to combat artemis inin resistance.
Abstract: Artemisinin-based combination therapies are the most effective drugs to treat Plasmodium falciparum malaria. Reduced sensitivity to artemisinin monotherapy, coupled with the emergence of parasite resistance to all partner drugs, threaten to place millions of patients at risk of inadequate treatment of malaria. Recognizing the significance and immediacy of this possibility, the Fogarty International Center and the National Institute of Allergy and Infectious Diseases of the U.S. National Institutes of Health convened a conference in November 2010 to bring together the diverse array of stakeholders responding to the growing threat of artemisinin resistance, including scientists from malarious countries in peril. This conference encouraged and enabled experts to share their recent unpublished data from studies that may improve our understanding of artemisinin resistance. Conference sessions addressed research priorities to forestall artemisinin resistance and fostered collaborations between field- and laboratory-based researchers and international programs, with the aim of translating new scientific evidence into public health solutions. Inspired by this conference, this review summarizes novel findings and perspectives on artemisinin resistance, approaches for translating research data into relevant public health information, and opportunities for interdisciplinary collaboration to combat artemisinin resistance.

157 citations


Journal ArticleDOI
TL;DR: The estimated density of infected nymphs (mDIN) was significantly correlated with human incidence and the relationship was strongest in high-prevalence areas, but it varied by region and state, partly because of the distribution of B. burgdorferi genotypes.
Abstract: Prevention and control of Lyme disease is difficult because of the complex biology of the pathogen's (Borrelia burgdorferi) vector (Ixodes scapularis) and multiple reservoir hosts with varying degrees of competence. Cost-effective implementation of tick- and host-targeted control methods requires an understanding of the relation- ship between pathogen prevalence in nymphs, nymph abundance, and incidence of human cases of Lyme disease. We quantified the relationship between estimated acarological risk and human incidence using county-level human case data and nymphal prevalence data from field-derived estimates in 36 eastern states. The estimated density of infected nymphs (mDIN) was significantly correlated with human incidence (r = 0.69). The relationship was strongest in high- prevalence areas, but it varied by region and state, partly because of the distribution of B. burgdorferi genotypes. More information is needed in several high-prevalence states before DIN can be used for cost-effectiveness analyses.

150 citations


Journal ArticleDOI
TL;DR: A 384-well, high-throughput imaging assay for the detection of new anti-malarial compounds, which was initially validated by screening a marine natural product library, and subsequently used to screen more than 3 million data points from a variety of compound sources.
Abstract: 1Deaths associated with the disease occur predominantly in sub-Saharan Africa; however, Asia, Latin America, and the Middle East are also affected to varying degrees. 2 The causative agent is a parasite belonging to the genus Plasmodium , with the majority of deaths occurring with Plasmodium falciparum infection. The parasite develops by asexual replication in the human host and sexual differentiation in the Anopheles mosquito. 3 Sporozoites, transmitted to the human host by a mosquito bite; infect human liver cells giving rise to merozoites that invade circulating erythrocytes. The asexual blood stage of their life cycle involves the development from ring stage parasites to trophozoites, which then mature into schizonts containing daughter merozoites. Upon schizont rupture, merozoites are again released into the blood stream, which infect new erythrocytes in a cycle that takes ~48 hours to complete. Although a small proportion of the parasites differentiate into the sexual erythrocytic form, gametocytes, which are taken up by the mosquito to undergo sexual development. It is the blood stage parasites that are responsible for the clinical manifestations of the disease, thus the focus of the most current drug discovery programs . Parasite resistance to anti-malarial drugs has become major impedance in the treatment of malaria. The chemical diversity of the recognized anti-malarial drugs to date is limited, consisting of four major classes of compounds, namely aminoquinolines, antifolates, artemisinin derivatives, and hydroxynapthoquinones. 4 The concern, with respect to this limited chemical diversity, is that combination therapy of “new” drugs based on the known chemistry backbones will suffer from parasite resistance within a short period of time, caused by priming of the parasite by the “existing” drug. Sequencing of the P. falciparum genome has also demonstrated over 5,000 genes comprising a large number of diverse drug targets, many of which have yet to be characterized. 5 However, most of the current drugs to date interact with only a small selection of these drug targets including heme detoxification (chloroquine), folate metabolism, and the parasite’s mitochondria (atovaquone). 6

133 citations


Journal ArticleDOI
TL;DR: The results of semi-structured interviews with 15 international stakeholders, selected because of their experiences in CHW program implementation, to elicit their views on strategies that could increase CHW motivation and retention are reported.
Abstract: Despite resurgence in the use of community health workers (CHWs) in the delivery of community case management of childhood illnesses, a paucity of evidence for effective strategies to address key constraints of worker motivation and retention endures. This work reports the results of semi-structured interviews with 15 international stakeholders, selected because of their experiences in CHW program implementation, to elicit their views on strategies that could increase CHW motivation and retention. Data were collected to identify potential interventions that could be tested through a randomized control trial. Suggested interventions were organized into thematic areas; cross-cutting approaches, recruitment, training, supervision, incentives, community involvement and ownership, information and data management, and mHealth. The priority interventions of stakeholders correspond to key areas of the work motivation and CHW literature. Combined, they potentially provide useful insight for programmers engaging in further enquiry into the most locally relevant, acceptable, and evidence-based interventions.

Journal ArticleDOI
TL;DR: Recent developments to decrease the cost and run time, and increase the ease of use of NAT while maintaining their high sensitivity and specificity and low limit of detection at the point-of-care are described.
Abstract: Malaria remains a serious disease in the developing world. There is a growing consensus that new diagnostics are needed in low-resource settings. The ideal malaria diagnostic should be able to speciate; measure parasitemia; low-cost, quick, and simple to use; and capable of detecting low-level infections. A promising development are nucleic acid tests (NATs) for the diagnosis of malaria, which are well suited for point-of-care use because of their ability to detect low-level infections and speciate, and because they have high sensitivity and specificity. The greatest barrier to NAT use in the past has been its relatively high cost, and the amount of infrastructure required in the form of equipment, stable power, and reagent storage. This review describes recent developments to decrease the cost and run time, and increase the ease of use of NAT while maintaining their high sensitivity and specificity and low limit of detection at the point-of-care.

Journal ArticleDOI
TL;DR: CHIKV infection is an important but unrecognized cause of febrile illness in northern Tanzania and is more common among infants and children than adults and adolescents and among HIV-infected patients with severe immunosuppression.
Abstract: Consecutive febrile admissions were enrolled at two hospitals in Moshi, Tanzania. Confirmed acute Chikungunya virus (CHIKV), Dengue virus (DENV), and flavivirus infection were defined as a positive polymerase chain reaction (PCR) result. Presumptive acute DENV infection was defined as a positive anti-DENV immunoglobulin M (IgM) enzyme-linked immunsorbent assay (ELISA) result, and prior flavivirus exposure was defined as a positive anti-DENV IgG ELISA result. Among 870 participants, PCR testing was performed on 700 (80.5%). Of these, 55 (7.9%) had confirmed acute CHIKV infection, whereas no participants had confirmed acute DENV or flavivirus infection. Anti-DENV IgM serologic testing was performed for 747 (85.9%) participants, and of these 71 (9.5%) had presumptive acute DENV infection. Anti-DENV IgG serologic testing was performed for 751 (86.3%) participants, and of these 80 (10.7%) had prior flavivirus exposure. CHIKV infection was more common among infants and children than adults and adolescents (odds ratio [OR] 1.9, P = 0.026) and among HIV-infected patients with severe immunosuppression (OR 10.5, P = 0.007). CHIKV infection is an important but unrecognized cause of febrile illness in northern Tanzania. DENV or other closely related flaviviruses are likely also circulating.

Journal ArticleDOI
TL;DR: Mosquito abundance was correlated with weather parameters, including temperature indices, and potential larval development sites were abundant in Puebla City and other high-elevation communities, suggesting that Ae.
Abstract: Mexico has cities (e.g., Mexico City and Puebla City) located at elevations > 2,000 m and above the elevation ceiling below which local climates allow the dengue virus mosquito vector Aedes aegypti to proliferate. Climate warming could raise this ceiling and place high-elevation cities at risk for dengue virus transmission. To assess the elevation ceiling for Ae. aegypti and determine the potential for using weather/climate parameters to predict mosquito abundance, we surveyed 12 communities along an elevation/climate gradient from Veracruz City (sea level) to Puebla City (∼2,100 m). Ae. aegypti was commonly encountered up to 1,700 m and present but rare from 1,700 to 2,130 m. This finding extends the known elevation range in Mexico by > 300 m. Mosquito abundance was correlated with weather parameters, including temperature indices. Potential larval development sites were abundant in Puebla City and other high-elevation communities, suggesting that Ae. aegypti could proliferate should the climate become warmer.

Journal ArticleDOI
TL;DR: It appears that dogs have a role in human hookworm transmission and warrant further investigation, and strong heterogeneity for helminthiasis by ethnicity, province, and wealth status coincided with a risk profile demonstrating that Mon-Khmer persons and the poorest households are highly vulnerable.
Abstract: We conducted a community cross-sectional survey of soil-transmitted helminthiasis in humans and dogs in four provinces in northern Laos. We collected and tested human and dog fecal samples and analyzed results against sociodemographic data. The prevalence of Ascaris lumbricoides, Trichuris trichiura, hookworm, and Strongyloides stercoralis was 26.1% (95% confidence interval [CI] = 23.7–28.4%), 41.5% (95% CI = 38.8–44.1%), 46.3% (95% CI = 43.3–49.0%), and 8.9% (95% CI = 7.4–10.4%), respectively. We observed strong heterogeneity for helminthiasis by ethnicity, province, and wealth status, which coincided with a risk profile demonstrating that Mon-Khmer persons and the poorest households are highly vulnerable. Necator americanus was the dominant hookworm species infecting humans and Ancylostoma ceylanicum was the only Ancylostoma species detected. Hookworm prevalence in village dogs was 94%, and the dominant species was A. ceylanicum. Necator americanus was also detected in dogs. It appears that dogs have a role in human hookworm transmission and warrant further investigation.

Journal ArticleDOI
TL;DR: Two novel mechanistic measures of transmission risk, the temperature-dependent ratio of virus extrinsic incubation period to the mosquito gonotrophic period (BT) and the fundamental reproductive ratio (R(0)), were compared based on a mathematical model to analyze spatiotemporal patterns of receptivity to viral amplification.
Abstract: Temperature has played a critical role in the spatiotemporal dynamics of West Nile virus transmission throughout California from its introduction in 2003 through establishment by 2009. We compared two novel mechanistic measures of transmission risk, the temperature-dependent ratio of virus extrinsic incubation period to the mosquito gonotrophic period (BT), and the fundamental reproductive ratio (R0) based on a mathematical model, to analyze spatiotemporal patterns of receptivity to viral amplification. Maps of BT and R0 were created at 20-km scale and compared throughout California to seroconversions in sentinel chicken flocks at half-month intervals. Overall, estimates of BT and R0 agreed with intensity of transmission measured by the frequency of sentinel chicken seroconversions. Mechanistic measures such as these are important for understanding how temperature affects the spatiotemporal dynamics of West Nile virus transmission and for delineating risk estimates useful to inform vector control agency intervention decisions and communicate outbreak potential.

Journal ArticleDOI
TL;DR: Efforts to increase usage of school latrines by constructing new facilities may pose a risk to children in the absence of sufficient hygiene behavior change, daily provision of soap and water, and anal cleansing materials.
Abstract: Handwashing with soap effectively reduces exposure to diarrhea-causing pathogens. Interventions to improve hygiene and sanitation conditions in schools within low-income countries have gained increased attention; however, their impact on schoolchildren's exposure to fecal pathogens has not been established. Our trial examined whether a school-based water, sanitation, and hygiene intervention reduced Escherichia coli contamination on pupils' hands in western Kenya. A hygiene promotion and water treatment intervention did not reduce risk of E. coli presence (relative risk (RR) = 0.92, 95% confidence interval (CI) = 0.54-1.56); the addition of new latrines to intervention schools significantly increased risk among girls (RR = 2.63, 95% CI = 1.29-5.34), with a non-significant increase among boys (RR = 1.36, 95% CI = 0.74-2.49). Efforts to increase usage of school latrines by constructing new facilities may pose a risk to children in the absence of sufficient hygiene behavior change, daily provision of soap and water, and anal cleansing materials.

Journal ArticleDOI
TL;DR: Survey data suggest nonfatal exposure of persons to rabies virus, which is likely associated with vampire bat depredation.
Abstract: In May of 2010, two communities (Truenococha and Santa Marta) reported to be at risk of vampire bat depredation were surveyed in the Province Datem del Maranon in the Loreto Department of Peru. Risk factors for bat exposure included age less than or equal to 25 years and owning animals that had been bitten by bats. Rabies virus neutralizing antibodies (rVNAs) were detected in 11% (7 of 63) of human sera tested. Rabies virus ribonucleoprotein (RNP) immunoglobulin G (IgG) antibodies were detected in the sera of three individuals, two of whom were also seropositive for rVNA. Rabies virus RNP IgM antibodies were detected in one respondent with no evidence of rVNA or RNP IgG antibodies. Because one respondent with positive rVNA results reported prior vaccination and 86% (six of seven) of rVNA-positive respondents reported being bitten by bats, these data suggest nonfatal exposure of persons to rabies virus, which is likely associated with vampire bat depredation.

Journal ArticleDOI
TL;DR: It is concluded that appropriately trained and supervised CHWs can use RDTs safely and accurately in community practice for up to 12 months post-training.
Abstract: Malaria rapid diagnostic tests (RDTs) could radically improve febrile illness management in remote and low-resource populations. However, reliance upon community health workers (CHWs) remains controversial because of concerns about blood safety and appropriate use of artemisinin combination therapy. This study assessed CHW ability to use RDTs safely and accurately up to 12 months post-training. We trained 65 Zambian CHWs, and then provided RDTs, job-aids, and other necessary supplies for village use. Observers assessed CHW performance at 3, 6, and 12 months post-training. Critical steps performed correctly increased from 87.5% at 3 months to 100% subsequently. However, a few CHWs incorrectly read faint positive or invalid results as negative. Although most indicators improved or remained stable over time, interpretation of faint positives fell to 76.7% correct at 12 months. We conclude that appropriately trained and supervised CHWs can use RDTs safely and accurately in community practice for up to 12 months post-training.

Journal ArticleDOI
TL;DR: Dengue, endemic in Puerto Rico, reached a record high in 2010 and annual economic cost was $46.45 million ($12.47 per capita), and work absenteeism because of a dengue episode exceeded the absenteeism for an episode of influenza or acute otitis media.
Abstract: Dengue, endemic in Puerto Rico, reached a record high in 2010. To inform policy makers, we derived annual economic cost. We assessed direct and indirect costs of hospitalized and ambulatory dengue illness in 2010 dollars through surveillance data and interviews with 100 laboratory-confirmed dengue patients treated in 2008-2010. We corrected for underreporting by using setting-specific expansion factors. Work absenteeism because of a dengue episode exceeded the absenteeism for an episode of influenza or acute otitis media. From 2002 to 2010, the aggregate annual cost of dengue illness averaged $38.7 million, of which 70% was for adults (age 15+ years). Hospitalized patients accounted for 63% of the cost of dengue illness, and fatal cases represented an additional 17%. Households funded 48% of dengue illness cost, the government funded 24%, insurance funded 22%, and employers funded 7%. Including dengue surveillance and vector control activities, the overall annual cost of dengue was $46.45 million ($12.47 per capita).

Journal ArticleDOI
TL;DR: The data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia and help guide public health responses in developing nations.
Abstract: The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations.

Journal ArticleDOI
TL;DR: In this article, Schistosoma mansoni infection was found to increase risk of human immunodeficiency virus (HIV) acquisition in women in rural Tanzanian villages near Lake Victoria, where S. mansoni is hyperendemic for sexually transmitted infections (STIs) and schistosomiasis.
Abstract: Animal and human studies suggest that Schistosoma mansoni infection may increase risk of human immunodeficiency virus (HIV) acquisition. Therefore, we tested 345 reproductive age women in rural Tanzanian villages near Lake Victoria, where S. mansoni is hyperendemic, for sexually transmitted infections (STIs) and schistosomiasis by circulating anodic antigen (CAA) serum assay. Over one-half (54%) had an active schistosome infection; 6% were HIV-seropositive. By univariate analysis, only schistosome infection predicted HIV infection (odds ratio [OR] = 3.9, 95% confidence interval = [1.3-12.0], P = 0.015) and remained significant using multivariate analysis to control for age, STIs, and distance from the lake (OR = 6.2 [1.7-22.9], P = 0.006). HIV prevalence was higher among women with more intense schistosome infections (P = 0.005), and the median schistosome intensity was higher in HIV-infected than -uninfected women (400 versus 15 pg CAA/mL, P = 0.01). This finding suggests that S. mansoni infection may be a modifiable HIV risk factor that places millions of people worldwide at increased risk of HIV acquisition.

Journal ArticleDOI
TL;DR: This validated, internally controlled qRT-PCR method also uses a small sample volume requiring minimal pre-analytical handling, making it useful for clinical trials, and determined that A-type 18S rRNAs are stably expressed at 1 × 10(4) copies per ring-stage parasite.
Abstract: To detect pre-patent parasitemia, we developed a real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for the asexual 18S ribosomal RNA (rRNAs) of Plasmodium falciparum. Total nucleic acids extracted from whole blood were combined with control RNA and tested by qRT-PCR. The assay quantified > 98.7% of parasite-containing samples to ±0.5 log10 parasites/mL of the nominal value without false positives. The analytical sensitivity was ³ 20 parasites/mL. The coefficient of variation was 0.6% and 1.8% within runs and 1.6% and 4.0% between runs for high and low parasitemia specimens, respectively. Using this assay, we determined that A-type 18S rRNAs are stably expressed at 1 ´ 10 4 copies per ring-stage parasite. When used to monitor experimental P. falciparum infection of human volunteers, the assay detected blood-stage infections 3.7 days earlier on average than thick blood smears. This validated, internally controlled qRT-PCR method also uses a small (50 µL) sample volume requiring mini- mal pre-analytical handling, making it useful for clinical trials.

Journal ArticleDOI
TL;DR: This effectiveness trial conducted in Burkina Faso, Ghana, and Uganda, compared a diagnostic and treatment package for malaria and pneumonia with presumptive treatment with anti-malarial drugs; artemisinin combination therapy (ACT).
Abstract: Evidence on the impact of using diagnostic tests in community case management of febrile children is limited. This effectiveness trial conducted in Burkina Faso, Ghana, and Uganda, compared a diagnostic and treatment package for malaria and pneumonia with presumptive treatment with anti-malarial drugs; artemisinin combination therapy (ACT). We enrolled 4,216 febrile children between 4 and 59 months of age in 2009-2010. Compliance with the malaria rapid diagnostic test (RDT) results was high in the intervention arm across the three countries, with only 4.9% (17 of 344) of RDT-negative children prescribed an ACT. Antibiotic overuse was more common: 0.9% (4 of 446) in Uganda, 38.5% (114 of 296) in Burkina Faso, and 44.6% (197 of 442) in Ghana. Fever clearance was high in both intervention and control arms at both Day 3 (97.8% versus 96.9%, P = 0.17) and Day 7 (99.2% versus 98.8%, P = 0.17). The use of diagnostic tests limits overuse of ACTs. Its impact on antibiotic overuse and on fever clearance is uncertain.

Journal ArticleDOI
TL;DR: In the presence of polymerase chain reaction-proven acute dengue infections, it is suggested a complete blood count and rapid measurement of IL-10 can assist in the triage of potential DHF cases for close follow-up or clinical intervention improving clinical outcome.
Abstract: Dengue virus infections are a major cause of morbidity in tropical countries. Early detection of dengue hemorrhagic fever (DHF) may help identify individuals that would benefit from intensive therapy. Predictive modeling was performed using 11 laboratory values of 51 individuals (38 DF and 13 DHF) obtained on initial presentation using logistic regression. We produced a robust model with an area under the curve of 0.9615 that retained IL-10 levels, platelets, and lymphocytes as the major predictive features. A classification and regression tree was developed on these features that were 86% accurate on cross-validation. The IL-10 levels and platelet counts were also identified as the most informative features associated with DHF using a Random Forest classifier. In the presence of polymerase chain reaction-proven acute dengue infections, we suggest a complete blood count and rapid measurement of IL-10 can assist in the triage of potential DHF cases for close follow-up or clinical intervention improving clinical outcome.

Journal ArticleDOI
TL;DR: Most anemia was caused by factors that could be prevented by available tools, stressing the need to reinforce their implementation and to evaluate their effectiveness throughout the course of the pregnancy.
Abstract: The risk factors for maternal anemia (hemoglobin level less than 110 g/L) were studied in human immunodeficiency virus-negative pregnant women in Benin at the time of first antenatal visit and prior to any prevention. Data for the first 1,005 pregnant women included in a multicentre randomized controlled trial were analyzed. Anemia was common (68.3%), and malaria and helminth infestations were prevalent in 15.2% and 11.1% of the women. A total of 33.3%, 31.3% and 3.6% of the women were iron, folic acid and vitamin B12 deficient, respectively. These parasitic infections and nutrient deficiencies were associated with a high risk of anemia. Twenty-one percent, 15%, 12%, 11% and 7% of anemia were attributable to malnutrition, malaria, iron, folic acid deficiencies, and helminth infestations, respectively. Most anemia was caused by factors that could be prevented by available tools, stressing the need to reinforce their implementation and to evaluate their effectiveness throughout the course of the pregnancy.

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TL;DR: There is a high prevalence of anemia in children, and their nutritional status is quite poor, and humanitarians and governments should launch comprehensive interventions to control anemia.
Abstract: Anemia is a common nutritional problem, and it has a remarkably high prevalence rate in Southeast Asia. In this study, children from 6 to 36 months were investigated to determine (1) the prevalence of anemia and (2) risk factors associated with anemia. Convenience sampling was used to select three villages in three different regions in Burma. Hemoglobin and anthropometric indicators were measured for 872 children. Logistic regression analyses were used to determine factors associated with anemia. The overall prevalence of anemia was 72.6%, with 40.0% having severe anemia. Predictors of anemia are a young age (P < 0.001), mother with anemia (P < 0.001), height-for-age Z score < -2 (P = 0.017), low family income (P < 0.001), mothers without primary education (P = 0.007), drinking unboiled water (P = 0.029), and fever in the last 3 months (P = 0.001). There is a high prevalence of anemia in children, and their nutritional status is quite poor. To control anemia, humanitarians and governments should launch comprehensive interventions.

Journal ArticleDOI
TL;DR: Management of common childhood illness at private sector drug shops in rural Uganda is largely inappropriate and there is urgent need to improve the standard of care at drug shops for common Childhood illness through public–private partnerships.
Abstract: We conducted a survey involving 1,604 households to determine community care-seeking patterns and 163 exit interviews to determine appropriateness of treatment of common childhood illnesses at private sector drug shops in two rural districts of Uganda. Of children sick within the last 2 weeks, 496 (53.1%) children first sought treatment in the private sector versus 154 (16.5%) children first sought treatment in a government health facility. Only 15 (10.3%) febrile children treated at drug shops received appropriate treatment for malaria. Five (15.6%) children with both cough and fast breathing received amoxicillin, although no children received treatment for 5-7 days. Similarly, only 8 (14.3%) children with diarrhea received oral rehydration salts, but none received zinc tablets. Management of common childhood illness at private sector drug shops in rural Uganda is largely inappropriate. There is urgent need to improve the standard of care at drug shops for common childhood illness through public-private partnerships.

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TL;DR: Results further support the use of B. bassiana as a potential biocontrol agent against Ae.
Abstract: The fungus Beauveria bassiana reduces Aedes aegypti longevity in laboratory conditions, but effects on survival, blood-feeding behavior, and fecundity in realistic environmental conditions have not been tested. Adult, female Ae. aegypti infected with B. bassiana (FI-277) were monitored for blood-feeding success and fecundity in the laboratory. Fungal infection reduced mosquito-human contact by 30%. Fecundity was reduced by (mean ± SD) 29.3 ± 8.6 eggs per female per lifetime in the laboratory; egg batch size and viability were unaffected. Mosquito survival, blood-feeding behavior, and fecundity were also tested in 5 meter×7 meter×4 meter semi-field cages in northern Queensland, Australia. Fungal infection reduced mosquito survival in semi-field conditions by 59–95% in large cages compared with 61–69% in small cages. One semi-field cage trial demonstrated 80% reduction in blood-feeding; a second trial showed no significant effect. Infection did not affect fecundity in large cages. Beauveria bassiana can kill and may reduce biting of Ae. aegypti in semi-field conditions and in the laboratory. These results further support the use of B. bassiana as a potential biocontrol agent against Ae. aegypti.

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TL;DR: This is the first report on confirmation of Nipah viral RNA in Pteropus bat from India and suggests the possible role of this species in transmission of NiV in India.
Abstract: The study deals with the survey of different bat populations (Pteropus giganteus, Cynopterus sphinx, and Megaderma lyra) in India for highly pathogenic Nipah virus (NiV), Reston Ebola virus, and Marburg virus. Bats (n = 140) from two states in India (Maharashtra and West Bengal) were tested for IgG (serum samples) against these viruses and for virus RNAs. Only NiV RNA was detected in a liver homogenate of P. giganteus captured in Myanaguri, West Bengal. Partial sequence analysis of nucleocapsid, glycoprotein, fusion, and phosphoprotein genes showed similarity with the NiV sequences from earlier outbreaks in India. A serum sample of this bat was also positive by enzyme-linked immunosorbent assay for NiV-specific IgG. This is the first report on confirmation of Nipah viral RNA in Pteropus bat from India and suggests the possible role of this species in transmission of NiV in India.