Sundeep Gupta

Outbreak of Salmonella Braenderup infections associated with Roma tomatoes, northeastern United States, 2004: a useful method for subtyping exposures in field investigations.

Salmonella Braenderup is an uncommon serotype in the United States. In July 2004, a multistate outbreak of Salmonella Braenderup diarrhoeal infections occurred, with 125 clinical isolates identified. To investigate, we conducted a case-control study, enrolling 32 cases and 63 matched controls. Cheese, lettuce and tomato eaten at restaurants all appeared to be associated with illness. To further define specific exposures, we conducted a second study and asked managers of restaurants patronized by patients and controls about cheese, lettuce and tomato varieties used in dishes their patrons reported consuming. This information was obtained for 27 cases and 29 controls. Roma tomatoes were the only exposure significantly associated with illness (odds ratio 4.3, 95% confidence interval 1.2-15.9). Roma tomatoes from two restaurants were traced back to a single tomato packing house. The methods used in this field investigation to define specific exposures may be useful for other foodborne outbreaks.

Part I. Analysis of data gaps pertaining to Salmonella enterica serotype Typhi infections in low and medium human development index countries, 1984-2005.

There are only 10 contemporary, population-based studies of typhoid fever that evaluate disease incidence using blood culture for confirmation of cases. Reported incidence ranged from 13 to 976/100 000 persons per year. These studies are likely to have been done preferentially in high- incidence sites which makes generalization of data difficult. Only five of these studies reported mortality. Of these the median (range) mortality was 0% (0-1.8%). Since study conditions usually involved enhanced clinical management of patients and the studies were not designed to evaluate mortality as an outcome, their usefulness for generalizing case-fatality rates is uncertain. No contemporary population-based studies reported rates of complications. Hospital-based typhoid fever studies reported median (range) complication rates of 2.8% (0.6-4.9%) for intestinal perforation and case-fatality rates of 2.0% (0-14.8%). Rates of complications other than intestinal perforation were not reported in contemporary hospital-based studies. Hospital-based studies capture information on the most severe illnesses among persons who have access to health-care services limiting their generalizability. Only two studies have informed the current understanding of typhoid fever age distribution curves. Extrapolation from population-based studies suggests that most typhoid fever occurs among young children in Asia. To reduce gaps in the current understanding of typhoid fever incidence, complications, and case-fatality rate, large population-based studies using blood culture confirmation of cases are needed in representative sites, especially in low and medium human development index countries outside Asia.

Comparison of home and clinic-based HIV testing among household members of persons taking antiretroviral therapy in Uganda: results from a randomized trial.

Objective:Due to high rates of undiagnosed and untreated HIV infection in Africa, we compared HIV counseling and testing (VCT) uptake among household members of patients receiving antiretroviral therapy. Methods:HIV-infected persons attending an AIDS clinic were randomized to a home-based or clinic-based antiretroviral therapy program including VCT for household members. Clinic arm participants were given free VCT vouchers and encouraged to invite their household members to the clinic for VCT. Home arm participants were visited, and their household members offered VCT using a 3-test rapid finger-stick testing algorithm. VCT uptake and HIV prevalence were compared. Findings:Of 7184 household members, 3974 (55.3%) were female and 4798 (66.8%) were in the home arm. Home arm household members were more likely to receive VCT than those from the clinic arm (55.8% vs. 10.9%, odds ratio: 10.41, 95% confidence interval: 7.89 to 13.73; P < 0.001), although the proportion of HIV-infected household members was higher in the clinic arm (17.3% vs. 7.1%, odds ratio: 2.76, 95% confidence interval: 1.97 to 3.86, P < 0.001). HIV prevalence among all household members tested in the home arm was 56% compared with 27% in the clinic arm. Of 148 spouses of HIV-infected patients, 69 (46.6%) were uninfected. Persons aged 15-24 were less likely to test than other age groups, and in the home arm, women were more likely to test than men. Conclusions:Home-based VCT for household members of HIV-infected persons was feasible, associated with lower prevalence, higher uptake, and increased identification of HIV-infected persons than clinic-based provision.

Tubewell water quality and predictors of contamination in three flood-prone areas in Bangladesh

Aims:  To measure enteric bacterial contamination of tubewells in three flood prone areas in Bangladesh and the relationship of bacteriological contamination with tubewell sanitary inspection scores.

Laboratory-Based Surveillance of Paratyphoid Fever in the United States : Travel and Antimicrobial Resistance

BACKGROUND The incidence of paratyphoid fever, including paratyphoid fever caused by antimicrobial-resistant strains, is increasing globally. However, the epidemiologic and laboratory characteristics of paratyphoid fever in the United States have never been studied. METHODS We attempted to interview all patients who had been infected with laboratory-confirmed Salmonella serotypes Paratyphi A, Paratyphi B, or Paratyphi C in the United States with specimens collected from 1 April 2005 through 31 March 2006. At the Centers for Disease Control and Prevention (CDC), isolates underwent serotype confirmation, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis typing. RESULTS Of 149 patients infected with Salmonella Paratyphi A, we obtained epidemiologic information for 89 (60%); 55 (62%) of 86 were hospitalized. Eighty-five patients (96%) reported having travel internationally, and 80 (90%) had traveled to South Asia. Of the 146 isolates received at the CDC, 127 (87%) were nalidixic acid resistant; nalidixic acid resistance was associated with travel to South Asia (odds ratio, 17.0; 95% confidence interval, 3.8-75.9). All nalidixic acid-resistant isolates showed decreased susceptibility to ciprofloxacin (minimum inhibitory concentration, > or = 0.12 microg/mL). Of 49 patients infected with Salmonella Paratyphi B, only 12 (24%) were confirmed to have Paratyphi B when tested at the CDC. Four (67%) of 6 patients were hospitalized, and 5 (83%) reported travel (4 to the Andean region of South America). One case of Salmonella Paratyphi C infection was reported in a traveler to West Africa with a urinary tract infection. CONCLUSIONS Physicians should be aware of the increasing incidence of infection due to Salmonella Paratyphi A and treatment options given its widespread antimicrobial resistance. A paratyphoid fever vaccine is urgently needed. Continued surveillance for paratyphoid fever will help guide future prevention and treatment recommendations.

Part II. Analysis of data gaps pertaining to Shigella infections in low and medium human development index countries, 1984–2005

The global incidence of Shigella infection has been estimated at 80-165 million episodes annually, with 99% of episodes occurring in the developing world. To identify contemporary gaps in the understanding of the global epidemiology of shigellosis, we conducted a review of the English-language scientific literature from 1984 to 2005, restricting the search to low and medium human development countries. Our review yielded 11 population-based studies of Shigella burden from seven countries. No population-based studies have been conducted in sub-Saharan Africa or in low human development countries. In studies done in all age groups, Shigella incidence varied from 0.6 to 107 episodes/1000 person-years. S. flexneri was the most commonly detected subgroup in the majority of studies. Case-fatality rates ranged from 0% to 2.6% in population-based studies and from 0% to 21% in facility-based studies. This review highlights the large gaps in data on the burden of Shigella infections for low human development index countries and, more specifically, for sub-Saharan Africa.

Human Herpesvirus 8 Infection in Children and Adults in a Population-based Study in Rural Uganda

BACKGROUND Human herpesvirus 8 (HHV-8) infection is endemic in sub-Saharan Africa. We examined sociodemographic, behavioral, and biological factors associated with HHV-8 infection in children and adults to determine HHV-8 seroprevalence and potential routes of transmission. METHODS Participants were 1383 children and 1477 adults from a population-based sample in a rural community in Uganda. Serum samples were tested for HHV-8 antibodies with use of an enzyme immunoassay against K8.1. RESULTS HHV-8 seroprevalence increased from 16% among children aged 1.5-2 years to 32% among children aged 10-13 years (P <.001) and from 37% among participants aged 14-19 years to 49% among adults aged ≥ 50 years (P <.05). HHV-8 seropositivity in children was independently associated with residing with a seropositive parent (P < .001) and residing with ≥ 1 other seropositive child aged <14 years (P < .001). History of sharing food and/or sauce plates was marginally associated with HHV-8 infection in children (P = .05). Among 1404 participants aged ≥ 15 years , there was no association between correlates of sexual behavior (eg, number of lifetime sex partners and HIV infection) and HHV-8 seropositivity (P > .10). CONCLUSIONS Our data suggest that HHV-8 is acquired primarily through horizontal transmission in childhood from intrafamilial contacts and that transmission continues into adulthood potentially through nonsexual routes.

High Rates of STD and Sexual Risk Behaviors Among Garífunas in Honduras

Background: Honduras has the highest concentration of HIV and AIDS cases in Central America, with an estimated adult HIV prevalence of 1.5%. Prevalence is higher among certain ethnic groups such as the Garífuna with a reported HIV prevalence of 8%. Methods: A biological and behavioral survey was conducted on a stratified random sample of the Garífuna population in Honduras, using computer-assisted interviews. Blood was tested for HIV, herpes simplex type 2 (HSV-2), and syphilis; urine was tested for Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis, and Mycoplasma genitalum. Results: We enrolled a total of 817 participants, 41% female and 51% male. Estimated prevalences and 95% confidence intervals (CI) were: HIV, 4.5% (95% CI: 3.0 to 6.6), HSV-2, 51.1% (95% CI: 46.7 to 55.6), and syphilis seropositivity, 2.4% (95% CI: 1.4 to 4.0). Sexually transmitted infections in urine were: chlamydia, 6.8% (95% CI: 4.7 to 9.7), gonorrhea, 1.1% (95% CI: 0.4 to 2.9), trichomoniasis, 10.5% (95% CI: 8.1 to 13.6), and Mycoplasma genitalium, 7.1% (95% CI: 5.1 to 9.9). Consistent condom use was low with stable (10.6%) and casual (41.4%) partners. In multivariate analysis, HIV was associated with rural residence. HSV-2 was associated with female sex, older age, and syphilis seropositivity. Conclusions: We found a moderate prevalence of HIV and a high prevalence of HSV-2 among the Garífunas. HSV-2 may increase the vulnerability of these populations to HIV in the future. Intervention strategies should emphasize sexually transmitted infection control and condom promotion, specifically targeting the Garífuna population.

On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings

Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers’ knowledge of a patients virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider perceptions of VL monitoring and indicate the importance of policies responsive to individual and environmental challenges of VL monitoring program implementation. Findings may inform scale-up by helping policy-makers identify strategies to improve feasibility and sustainability of VL monitoring.

Measures of viral load using Abbott RealTime HIV-1 Assay on venous and fingerstick dried blood spots from provider-collected specimens in Malawian District Hospitals

BACKGROUND Viral suppression is a key indicator of antiretroviral therapy (ART) response among HIV-infected patients. Dried blood spots (DBS) are an appealing alternative to conventional plasma-based virologic testing, improving access to monitoring in resource-limited settings. However, validity of DBS obtained from fingerstick in field settings remains unknown. OBJECTIVES Investigate feasibility and accuracy of DBS vs plasma collected by healthcare workers in real-world settings of remote hospitals in Malawi. Compare venous DBS to fingerstick DBS for identifying treatment failure. STUDY DESIGN We recruited patients from ART clinics at two district hospitals in Malawi, collecting plasma, venous DBS (vDBS), and fingerstick DBS (fsDBS) cards for the first 149 patients, and vDBS and fsDBS only for the subsequent 398 patients. Specimens were tested using Abbott RealTime HIV-1 Assay (lower detection limit 40 copies/ml (plasma) and 550 copies/ml (DBS)). RESULTS 21/149 (14.1%) had detectable viremia (>1.6 log copies/ml), 13 of which were detectable for plasma, vDBS, and fsDBS. Linear regression demonstrated high correlation for plasma vs. DBS (vDBS: β=1.19, R(2)=0.93 (p<0.0001); fsDBS β=1.20, R(2)=0.90 (p<0.0001)) and vDBS vs. fsDBS (β=0.88, R(2)=0.73, (p<0.0001)). Mean difference between plasma and vDBS was 1.1 log copies/ml [SD: 0.27] and plasma and fsDBS 1.1 log copies/ml [SD: 0.31]. At 5000 copies/ml, sensitivity was 100%, and specificity was 98.6% and 97.8% for vDBS and fsDBS, respectively, compared to plasma. CONCLUSIONS DBS from venipuncture and fingerstick perform well at the failure threshold of 5000 copies/ml. Fingerstick specimen source may improve access to virologic treatment monitoring in resource-limited settings given task-shifting in high-volume, low-resource facilities.