To identify risk factors and describe the pattern of spread of the 1997 cholera epidemic in a rur... more To identify risk factors and describe the pattern of spread of the 1997 cholera epidemic in a rural area (Ifakara) in southern Tanzania, we conducted a prospective hospital-based, matched case- control study, with analysis based on the first 180 cases and 360 matched controls. Bathing in the river, long distance to water source, and eating dried fish were significantly associated with risk for cholera. Toxigenic Vibrio cholerae O1, biotype El Tor, serotype Ogawa, was isolated in samples from Ifakara's main water source and patients' stools. DNA molecular analyses showed identical patterns for all isolates.
Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enteri... more Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enterica subsp. enterica serovar Typhi. The objective of the study was to detect additional typhoid fever cases through serological tests. A total of 1732 prolonged fever episodes were evaluated using three serological tests, Widal, Tubex and Typhidot-M in a typhoid fever endemic area of southern China. A case definition which included a positive Widal test (TO>or=80 & TH>A), a positive Tubex test (>or=4) and a positive Typhidot-M test, increased the detection of cases by more than twofold from 13 to 28 cases. The case definition has a specificity of 100% and a sensitivity of 39%. Case definitions based on combinations of serological tests can detect additional typhoid fever cases with higher specificity than a single serological test. Improved case detection is essential to understand the true disease burden and can help to boost the power of intervention trials.
Background: Tigecycline, a member of a new class of antimicrobials (glycylcyclines), has been sho... more Background: Tigecycline, a member of a new class of antimicrobials (glycylcyclines), has been shown to have potent broad spectrum activity against most commonly encountered species responsible for hospital acquired infections. Cross-resistance to several classes of antimicrobials is often seen in nosocomial pathogens. The T.E.S.T. program determined the in vitro activity of tigecycline against strains of Enterobacteriaceae cross-resistant to one or more of the following antimicrobials: amoxicillin-clavulanic acid, piperacillin-tazobactam, levofloxacin, ceftriaxone, cefepime, ampicillin, amikacin, minocycline, ceftazidime and imipenem. The isolates were collected from 335 investigational sties in 47 countries throughout 2004-2007. Methods: A total of 26,791 clinical Enterobacteriaceae were identified to the species level at each site and confirmed by the central laboratory. Minimum Inhibitory Concentrations (MICs) were determined by the local laboratory using broth microdilution panels. Antimicrobial resistance was interpreted according to CLSI breakpoints with TIG susceptible and resistant breakpoints defined as = 8 mcg/ml, respectively.
Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a significant bur... more Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a significant burden, especially among the poor in countries where these illnesses are endemic. Older-generation, parenteral, whole-cell vaccines against cholera and typhoid fever were abandoned in many countries as public health tools because of problems with insufficient protection and/or inadequate safety profiles. Modern-generation licensed vaccines are available for cholera and typhoid fever, but are not widely used by those in greatest need. A number of experimental candidates exist for all three diseases. Future research should focus on generating the evidence necessary to obtain a consensus on the deployment of existing vaccines against cholera and typhoid fever, and on clinical evaluation of pipeline vaccine candidates against all three diseases.
Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi ... more Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the...
To inform policy-makers about introduction of preventive interventions against typhoid, including... more To inform policy-makers about introduction of preventive interventions against typhoid, including vaccination. A population-based prospective surveillance design was used. Study sites where typhoid was considered a problem by local authorities were established in China, India, Indonesia, Pakistan and Viet Nam. Standardized clinical, laboratory, and surveillance methods were used to investigate cases of fever of >or= 3 days' duration for a one-year period. A total of 441,435 persons were under surveillance, 159,856 of whom were aged 5-15 years. A total of 21,874 episodes of fever were detected. Salmonella typhi was isolated from 475 (2%) blood cultures, 57% (273/475) of which were from 5-15 year-olds. The annual typhoid incidence (per 100,000 person years) among this age group varied from 24.2 and 29.3 in sites in Viet Nam and China, respectively, to 180.3 in the site in Indonesia; and to 412.9 and 493.5 in sites in Pakistan and India, respectively. Altogether, 23% (96/413) of...
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2015
The most common complication of herpes zoster (HZ) is postherpetic neuralgia (PHN), a persistent ... more The most common complication of herpes zoster (HZ) is postherpetic neuralgia (PHN), a persistent pain that can substantially affects quality of life (QoL). This analysis aimed to evaluate predictors of PHN in HZ patients. Pooled-analysis of prospective cohort studies of HZ patients ≥50 years from North America (Canada), Latin America (Brazil, Mexico and Argentina), and Asia (Taiwan, South Korea, and Thailand). Patients within 14 days of rash onset were included. PHN incidence was defined as worst pain score of ≥3, persisting/appearing >90 days after rash onset. Socio-demographics, HZ disease characteristics, treatment, pain-related interference with activities of daily living, and health-related QoL were assessed. Of 702 patients with HZ, 148 (21.1%) developed PHN. Similar risks of PHN were observed across geographic regions. In multivariate analysis, older age, greater severity of pain at rash onset, employment status, walking problems at enrollment, and pain interference affect...
The American journal of tropical medicine and hygiene, 1999
Malaria remains the most important parasitic cause of mortality in humans. Its presentation is th... more Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] = 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was ind...
The blood-brain barrier (BBB) constitutes a major obstacle in brain drug delivery. Focused ultras... more The blood-brain barrier (BBB) constitutes a major obstacle in brain drug delivery. Focused ultrasound (FUS) in conjunction with microbubbles has been shown to open the BBB noninvasively, locally, and transiently to allow large molecules diffusion. Neurturin (NTN), a member of the glial-derived neurotrophic factor (GDNF) family, has been demonstrated to have neuroprotective and regenerative effects on dopaminergic neurons in vivo using invasive drug delivery methods. The brain's ascending nigrostriatal pathway is severely damaged in Parkinson's disease (PD), and therefore the substantia nigra (SN) and striatal caudoputamen (CP) were selected as the target areas. The objective of the study was to investigate whether safe and efficient NTN delivery can be achieved through FUS-induced BBB opening via intravenous administration, and thus trigger the neuroregeneration cascade in the nigrostriatal pathway. After the optimization of FUS parameters and target locations in the murine brain, NTN bioavailability and downstream signaling were detected and characterized through immunostaining. FUS significantly enhanced the delivery of NTN compared with the direct injection technique, whereas triggering of the signaling cascade was detected downstream to the neuronal nuclei. These findings thus indicate the potential of the FUS method to mediate transport of proteins through the blood-brain barrier in a PD animal model.
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 2006
To estimate the fraction of fever and diarrhea patients making use of private practitioners, self... more To estimate the fraction of fever and diarrhea patients making use of private practitioners, self-treatment, hospital care, drug vendors, community health centers and traditional healers. A cross-sectional survey. Four slums in and around Karachi during October and November, 2001. A sample of 1842 households was selected with probability proportional to size of the slum. The household head or a representative was asked regarding the treatment providers for diarrhea and cases of fever persistent for 3 days or more. Only households with an actual case of fever and/or diarrhea were included in the analysis. The study found that more than half of diarrhea and fever cases are seen by private practitioners. Self medication with medicines available in the home or specifically purchased for the disease episode from a drug vendor combined provides 13% to 18% of health care. Only between 11% and 13% of patients are seen by the public sector, hospitals and community health centers. There was n...
To assess the herpes zoster (HZ) disease burden, including the severity and duration of HZ-associ... more To assess the herpes zoster (HZ) disease burden, including the severity and duration of HZ-associated pain, its impact on quality of life (QoL), and healthcare resource utilization (HCRU) in a South Korean clinical setting. Patients aged ≥50 years were followed prospectively for ≤6 months. Based on the duration of their episode at enrollment, cases were classified as incident (<7 days) or prevalent (≥7 days). HZ pain and discomfort were measured with the HZ Severity of Illness (HZ-SOI) severity-by-duration composite score. One hundred fifty-one patients (69.5% prevalent cases) were enrolled. Prodrome pain was experienced by 68.2% of patients, of whom 95.1% experienced moderate-to-severe pain; post-herpetic neuralgia was experienced by 38.4%. Prevalent disease, higher acute pain, and older age were significant predictors of greater HZ-SOI, while use of antivirals was associated with decreased HZ-SOI. HZ-associated pain was associated with reduced QoL and affected all daily living activities (particularly mood, life enjoyment, general activities, and sleep), resulting in significant HCRU, including primary care doctor, specialist, or physiotherapist consultations, hospitalizations, and emergency department visits. Severe morbidity, impaired QoL, and significant HCRU are associated with HZ in South Korea, especially in older patients, supporting the need for early intervention and preventive strategies to reduce the HZ-associated disease burden.
Journal of health, population, and nutrition, 2004
Many economic analyses of immunization programmes focus on the benefits in terms of public-sector... more Many economic analyses of immunization programmes focus on the benefits in terms of public-sector cost savings, but do not incorporate estimates of the private cost savings that individuals receive from vaccination. This paper considers the implications of Bahl et al.'s cost-of-illness estimates for typhoid immunization policy by examining how community-level incidence estimates and information on distribution of costs of illness among patients and the public-health sector can be used in the economic analysis of vaccination-programme options. The findings illustrate why typhoid vaccination programmes may often appear to be unattractive to public-health officials who adopt a public budgetary perspective. Under many plausible sets of assumptions, public-sector expenditure on typhoid vaccination does not yield comparable public-sector cost savings. If public-health officials adopt a societal perspective on the economic benefits of vaccination, there are many situations in which dif...
Journal of health, population, and nutrition, 2003
The objective of this study was to describe a mass-immunization campaign of a locally-produced or... more The objective of this study was to describe a mass-immunization campaign of a locally-produced oral, killed whole-cell cholera vaccine in Hue city, Vietnam. Mass immunization with a 2-dose regimen of the vaccine was conducted in 13 communes in early 1998. The total, age- and sex-specific vaccine coverage was calculated using data from the vaccination records and the government census. The number of vaccine doses procured, administered, wasted, and left over, and the human and other resources required to prepare and conduct the vaccination campaign were systematically recorded. Government expenditure for planning, procurement, and delivery of the vaccine were documented. In total, 118,555 (79%) of the 49,557 targeted population were fully vaccinated during the mass-vaccination campaign. The total expenditure for the project was US dollar 105,447, resulting in a cost per fully-vaccinated person of US dollar 0.89. Mass immunization with this locally-produced oral, killed cholera vaccin...
Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (... more Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+ IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases.
Since 2006, the vaccine, ZOSTAVAX(®), has been licensed to prevent herpes zoster. Only limited cl... more Since 2006, the vaccine, ZOSTAVAX(®), has been licensed to prevent herpes zoster. Only limited clinical follow-up data are available to evaluate duration of protection, an important consideration when developing HZ vaccination policy recommendations. Four Poisson regression models were developed based on an integrated analysis of data from the Shingles Prevention Study and its Short Term Persistence extension to estimate the effects of years-since-vaccination and chronological-age on vaccine efficacy among people ≥60 years old. The models included number of HZ cases parsed into categories by chronological-age and time-since-vaccination as the dependent variable with different explanatory variables in each model. In all models, the interaction between vaccine-group and chronological-age was statistically significant indicating that vaccine efficacy decreases with the expected effects of advancing age but the interaction between vaccine-group and time-since-vaccination was not statistically significant indicating that much of the reduction in vaccine efficacy over time-since-vaccination can be explained by increasing age.
Visits to household during a census in an impoverished area of north Jakarta were used for explor... more Visits to household during a census in an impoverished area of north Jakarta were used for exploring the four-week prevalence of diarrhoea, factors associated with episodes of diarrhoea, and the patterns of healthcare use. For 160,261 urban slum-dwellers, information was collected on the socioeconomic status of the household and on diarrhoea episodes of individual household residents in the preceding four
Journal of health, population, and nutrition, 2004
Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi ... more Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the...
One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccinat... more One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged < or = 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by...
To determine the safety and logistic feasibility of a mass immunization strategy outside the loca... more To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial...
Journal of health, population, and nutrition, 2004
Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to... more Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to facilitate the use of available anti-typhoid vaccines in developing countries. This one-year prospective surveillance was carried out in an urban slum community in Delhi, India, to estimate the costs of illness for cases of typhoid fever. Ninety-eight culture-positive typhoid, 31 culture-positive paratyphoid, and 94 culture-negative cases with clinical typhoid syndrome were identified during the surveillance. Estimates of costs of illness were based on data collected through weekly interviews conducted at home for three months following diagnosis. Private costs included the sum of direct medical, direct non-medical, and indirect costs. Non-patient (public) costs included costs of outpatient visits, hospitalizations, laboratory tests, and medicines provided free of charge to the families. The mean cost per episode of blood culture-confirmed typhoid fever was 3,597 Indian Rupees (US$ 1=IN...
To identify risk factors and describe the pattern of spread of the 1997 cholera epidemic in a rur... more To identify risk factors and describe the pattern of spread of the 1997 cholera epidemic in a rural area (Ifakara) in southern Tanzania, we conducted a prospective hospital-based, matched case- control study, with analysis based on the first 180 cases and 360 matched controls. Bathing in the river, long distance to water source, and eating dried fish were significantly associated with risk for cholera. Toxigenic Vibrio cholerae O1, biotype El Tor, serotype Ogawa, was isolated in samples from Ifakara's main water source and patients' stools. DNA molecular analyses showed identical patterns for all isolates.
Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enteri... more Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enterica subsp. enterica serovar Typhi. The objective of the study was to detect additional typhoid fever cases through serological tests. A total of 1732 prolonged fever episodes were evaluated using three serological tests, Widal, Tubex and Typhidot-M in a typhoid fever endemic area of southern China. A case definition which included a positive Widal test (TO>or=80 & TH>A), a positive Tubex test (>or=4) and a positive Typhidot-M test, increased the detection of cases by more than twofold from 13 to 28 cases. The case definition has a specificity of 100% and a sensitivity of 39%. Case definitions based on combinations of serological tests can detect additional typhoid fever cases with higher specificity than a single serological test. Improved case detection is essential to understand the true disease burden and can help to boost the power of intervention trials.
Background: Tigecycline, a member of a new class of antimicrobials (glycylcyclines), has been sho... more Background: Tigecycline, a member of a new class of antimicrobials (glycylcyclines), has been shown to have potent broad spectrum activity against most commonly encountered species responsible for hospital acquired infections. Cross-resistance to several classes of antimicrobials is often seen in nosocomial pathogens. The T.E.S.T. program determined the in vitro activity of tigecycline against strains of Enterobacteriaceae cross-resistant to one or more of the following antimicrobials: amoxicillin-clavulanic acid, piperacillin-tazobactam, levofloxacin, ceftriaxone, cefepime, ampicillin, amikacin, minocycline, ceftazidime and imipenem. The isolates were collected from 335 investigational sties in 47 countries throughout 2004-2007. Methods: A total of 26,791 clinical Enterobacteriaceae were identified to the species level at each site and confirmed by the central laboratory. Minimum Inhibitory Concentrations (MICs) were determined by the local laboratory using broth microdilution panels. Antimicrobial resistance was interpreted according to CLSI breakpoints with TIG susceptible and resistant breakpoints defined as = 8 mcg/ml, respectively.
Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a significant bur... more Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a significant burden, especially among the poor in countries where these illnesses are endemic. Older-generation, parenteral, whole-cell vaccines against cholera and typhoid fever were abandoned in many countries as public health tools because of problems with insufficient protection and/or inadequate safety profiles. Modern-generation licensed vaccines are available for cholera and typhoid fever, but are not widely used by those in greatest need. A number of experimental candidates exist for all three diseases. Future research should focus on generating the evidence necessary to obtain a consensus on the deployment of existing vaccines against cholera and typhoid fever, and on clinical evaluation of pipeline vaccine candidates against all three diseases.
Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi ... more Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the...
To inform policy-makers about introduction of preventive interventions against typhoid, including... more To inform policy-makers about introduction of preventive interventions against typhoid, including vaccination. A population-based prospective surveillance design was used. Study sites where typhoid was considered a problem by local authorities were established in China, India, Indonesia, Pakistan and Viet Nam. Standardized clinical, laboratory, and surveillance methods were used to investigate cases of fever of >or= 3 days' duration for a one-year period. A total of 441,435 persons were under surveillance, 159,856 of whom were aged 5-15 years. A total of 21,874 episodes of fever were detected. Salmonella typhi was isolated from 475 (2%) blood cultures, 57% (273/475) of which were from 5-15 year-olds. The annual typhoid incidence (per 100,000 person years) among this age group varied from 24.2 and 29.3 in sites in Viet Nam and China, respectively, to 180.3 in the site in Indonesia; and to 412.9 and 493.5 in sites in Pakistan and India, respectively. Altogether, 23% (96/413) of...
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2015
The most common complication of herpes zoster (HZ) is postherpetic neuralgia (PHN), a persistent ... more The most common complication of herpes zoster (HZ) is postherpetic neuralgia (PHN), a persistent pain that can substantially affects quality of life (QoL). This analysis aimed to evaluate predictors of PHN in HZ patients. Pooled-analysis of prospective cohort studies of HZ patients ≥50 years from North America (Canada), Latin America (Brazil, Mexico and Argentina), and Asia (Taiwan, South Korea, and Thailand). Patients within 14 days of rash onset were included. PHN incidence was defined as worst pain score of ≥3, persisting/appearing >90 days after rash onset. Socio-demographics, HZ disease characteristics, treatment, pain-related interference with activities of daily living, and health-related QoL were assessed. Of 702 patients with HZ, 148 (21.1%) developed PHN. Similar risks of PHN were observed across geographic regions. In multivariate analysis, older age, greater severity of pain at rash onset, employment status, walking problems at enrollment, and pain interference affect...
The American journal of tropical medicine and hygiene, 1999
Malaria remains the most important parasitic cause of mortality in humans. Its presentation is th... more Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] = 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was ind...
The blood-brain barrier (BBB) constitutes a major obstacle in brain drug delivery. Focused ultras... more The blood-brain barrier (BBB) constitutes a major obstacle in brain drug delivery. Focused ultrasound (FUS) in conjunction with microbubbles has been shown to open the BBB noninvasively, locally, and transiently to allow large molecules diffusion. Neurturin (NTN), a member of the glial-derived neurotrophic factor (GDNF) family, has been demonstrated to have neuroprotective and regenerative effects on dopaminergic neurons in vivo using invasive drug delivery methods. The brain&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s ascending nigrostriatal pathway is severely damaged in Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD), and therefore the substantia nigra (SN) and striatal caudoputamen (CP) were selected as the target areas. The objective of the study was to investigate whether safe and efficient NTN delivery can be achieved through FUS-induced BBB opening via intravenous administration, and thus trigger the neuroregeneration cascade in the nigrostriatal pathway. After the optimization of FUS parameters and target locations in the murine brain, NTN bioavailability and downstream signaling were detected and characterized through immunostaining. FUS significantly enhanced the delivery of NTN compared with the direct injection technique, whereas triggering of the signaling cascade was detected downstream to the neuronal nuclei. These findings thus indicate the potential of the FUS method to mediate transport of proteins through the blood-brain barrier in a PD animal model.
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 2006
To estimate the fraction of fever and diarrhea patients making use of private practitioners, self... more To estimate the fraction of fever and diarrhea patients making use of private practitioners, self-treatment, hospital care, drug vendors, community health centers and traditional healers. A cross-sectional survey. Four slums in and around Karachi during October and November, 2001. A sample of 1842 households was selected with probability proportional to size of the slum. The household head or a representative was asked regarding the treatment providers for diarrhea and cases of fever persistent for 3 days or more. Only households with an actual case of fever and/or diarrhea were included in the analysis. The study found that more than half of diarrhea and fever cases are seen by private practitioners. Self medication with medicines available in the home or specifically purchased for the disease episode from a drug vendor combined provides 13% to 18% of health care. Only between 11% and 13% of patients are seen by the public sector, hospitals and community health centers. There was n...
To assess the herpes zoster (HZ) disease burden, including the severity and duration of HZ-associ... more To assess the herpes zoster (HZ) disease burden, including the severity and duration of HZ-associated pain, its impact on quality of life (QoL), and healthcare resource utilization (HCRU) in a South Korean clinical setting. Patients aged ≥50 years were followed prospectively for ≤6 months. Based on the duration of their episode at enrollment, cases were classified as incident (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7 days) or prevalent (≥7 days). HZ pain and discomfort were measured with the HZ Severity of Illness (HZ-SOI) severity-by-duration composite score. One hundred fifty-one patients (69.5% prevalent cases) were enrolled. Prodrome pain was experienced by 68.2% of patients, of whom 95.1% experienced moderate-to-severe pain; post-herpetic neuralgia was experienced by 38.4%. Prevalent disease, higher acute pain, and older age were significant predictors of greater HZ-SOI, while use of antivirals was associated with decreased HZ-SOI. HZ-associated pain was associated with reduced QoL and affected all daily living activities (particularly mood, life enjoyment, general activities, and sleep), resulting in significant HCRU, including primary care doctor, specialist, or physiotherapist consultations, hospitalizations, and emergency department visits. Severe morbidity, impaired QoL, and significant HCRU are associated with HZ in South Korea, especially in older patients, supporting the need for early intervention and preventive strategies to reduce the HZ-associated disease burden.
Journal of health, population, and nutrition, 2004
Many economic analyses of immunization programmes focus on the benefits in terms of public-sector... more Many economic analyses of immunization programmes focus on the benefits in terms of public-sector cost savings, but do not incorporate estimates of the private cost savings that individuals receive from vaccination. This paper considers the implications of Bahl et al.'s cost-of-illness estimates for typhoid immunization policy by examining how community-level incidence estimates and information on distribution of costs of illness among patients and the public-health sector can be used in the economic analysis of vaccination-programme options. The findings illustrate why typhoid vaccination programmes may often appear to be unattractive to public-health officials who adopt a public budgetary perspective. Under many plausible sets of assumptions, public-sector expenditure on typhoid vaccination does not yield comparable public-sector cost savings. If public-health officials adopt a societal perspective on the economic benefits of vaccination, there are many situations in which dif...
Journal of health, population, and nutrition, 2003
The objective of this study was to describe a mass-immunization campaign of a locally-produced or... more The objective of this study was to describe a mass-immunization campaign of a locally-produced oral, killed whole-cell cholera vaccine in Hue city, Vietnam. Mass immunization with a 2-dose regimen of the vaccine was conducted in 13 communes in early 1998. The total, age- and sex-specific vaccine coverage was calculated using data from the vaccination records and the government census. The number of vaccine doses procured, administered, wasted, and left over, and the human and other resources required to prepare and conduct the vaccination campaign were systematically recorded. Government expenditure for planning, procurement, and delivery of the vaccine were documented. In total, 118,555 (79%) of the 49,557 targeted population were fully vaccinated during the mass-vaccination campaign. The total expenditure for the project was US dollar 105,447, resulting in a cost per fully-vaccinated person of US dollar 0.89. Mass immunization with this locally-produced oral, killed cholera vaccin...
Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (... more Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+ IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases.
Since 2006, the vaccine, ZOSTAVAX(®), has been licensed to prevent herpes zoster. Only limited cl... more Since 2006, the vaccine, ZOSTAVAX(®), has been licensed to prevent herpes zoster. Only limited clinical follow-up data are available to evaluate duration of protection, an important consideration when developing HZ vaccination policy recommendations. Four Poisson regression models were developed based on an integrated analysis of data from the Shingles Prevention Study and its Short Term Persistence extension to estimate the effects of years-since-vaccination and chronological-age on vaccine efficacy among people ≥60 years old. The models included number of HZ cases parsed into categories by chronological-age and time-since-vaccination as the dependent variable with different explanatory variables in each model. In all models, the interaction between vaccine-group and chronological-age was statistically significant indicating that vaccine efficacy decreases with the expected effects of advancing age but the interaction between vaccine-group and time-since-vaccination was not statistically significant indicating that much of the reduction in vaccine efficacy over time-since-vaccination can be explained by increasing age.
Visits to household during a census in an impoverished area of north Jakarta were used for explor... more Visits to household during a census in an impoverished area of north Jakarta were used for exploring the four-week prevalence of diarrhoea, factors associated with episodes of diarrhoea, and the patterns of healthcare use. For 160,261 urban slum-dwellers, information was collected on the socioeconomic status of the household and on diarrhoea episodes of individual household residents in the preceding four
Journal of health, population, and nutrition, 2004
Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi ... more Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the...
One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccinat... more One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged < or = 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by...
To determine the safety and logistic feasibility of a mass immunization strategy outside the loca... more To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial...
Journal of health, population, and nutrition, 2004
Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to... more Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to facilitate the use of available anti-typhoid vaccines in developing countries. This one-year prospective surveillance was carried out in an urban slum community in Delhi, India, to estimate the costs of illness for cases of typhoid fever. Ninety-eight culture-positive typhoid, 31 culture-positive paratyphoid, and 94 culture-negative cases with clinical typhoid syndrome were identified during the surveillance. Estimates of costs of illness were based on data collected through weekly interviews conducted at home for three months following diagnosis. Private costs included the sum of direct medical, direct non-medical, and indirect costs. Non-patient (public) costs included costs of outpatient visits, hospitalizations, laboratory tests, and medicines provided free of charge to the families. The mean cost per episode of blood culture-confirmed typhoid fever was 3,597 Indian Rupees (US$ 1=IN...
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Papers by Camilo Acosta