1999 Poster Competition Winners
Applied Research: 1st Prize
Paulo F. Barroso
Project Title: "Seminal HIV-1 Viral Load Is Reduced by Antiretroviral Therapy and Is Correlated with Plasma HIV-1 Viral Load"
Objective: To evaluate the correlation of SVL and PVL and the effect of ART in SVL in subjects starting ART in Brazil. Method: HIV-1 RNA was measured in plasma and whole semen by the Nuclisens(TM) assay before introduction of ART (BL) and at 1, 2, 3 and 6 months thereafter. Results: Correlation of SVL and PVL was statistically significant at all time points (p<0.0001). Spearman's rho were: BL: 0.46(n=103); 1 month: 0.44 (n=88); 2 months 0.62 (n=85); 3 months: 0.65 (n=88); 6 months: 0.65 (n=85). At baseline 27 of 103 (26%) of patients had undetectable SVL. This percentage increased after introduction of ART (67% at 1 month,71% at 2 months, 72% at 3 months and 75% at 6 months). At baseline the median PVL 42,000 cps/ml and the median SVL was 6,400 cps/ml. The reduction in SVL is reported for 69 patients who had detectable SVL and at least one follow-up measurement. Of those 59 (85%) were on double therapy and 10 (15%) were on triple therapy (including PI). The introduction of ART was associated with significative reductions in SVL and PVL. Mean reduction is SVL and PVL (in log (10), 95% CI and n) were: 1 month: 1.41 (1.17-1.64, n: 68) and 1.54 (1.31-1.76, n: 68); 2 months 1.53 (1.25-1.80, n: 64) and 1.63 (1.40-1.87, n: 65); 3 months 1.51 (1.20-1.81, n: 65) and 1.64 (1.38-1.91, n: 65) and 6 months 1.65 (1.34-1.96, n: 64) and 1.52 (1.25-1.79, n: 66). Conclusion: ART decreased SVL and the extent of this decline was similar to that of PVL. If associated with diminished transmissibility, these findings may have important implications for dynamics of the HIV epidemic.
Applied Research: 2nd Prize
Project Title: "Effects of El Nino phenomenon and ambient temperature on hospital admissions for diarrheal disease in Peruvian children"
There is growing concern the El Niño phenomenon, and more generally global warming, may harm the health of human populations. To investigate whether ambient temperature and El Niño had an effect on childhood diarrhea, we analyzed daily admissions for diarrhea to the Oral Rehydration Unit of the Instituto Nacional de Salud Del Nino in Lima, Peru, between January 1993 and November 1998. Our analytical method combined harmonic regression, semi-parametric curve fitting, and autoregressive-moving average models to assess the effect of El Niño on diarrheal admissions. During the 1997-98 El Niño event, daily ambient temperature in Lima increased as much as 5 °C above normal, and the number of daily admissions for diarrhea increased as much as 200 percent. For each degree centigrade of increase in mean ambient temperature, the number of diarrheal admissions increased 8 percent. The effects of ambient temperature and El Niño on the number of diarrheal admissions were greatest during the winter. We also found that El Niño had an effect on admissions greater than that explained by the increase in ambient temperature alone. Our results indicate that extreme climate variability such as those driven by El Niño episodes, or potentially long-tern global warming are likely to have strong effects on the epidemiology of diarrheal diseases. If our findings for Lima are reproducible in other regions, then cases of diarrhea may increase by millions worldwide with each degree of increase in ambient temperature above normal.
Applied Research: 3rd Prize
Project Title: "Role in treatment of malaria, patterns of patient referral, spatial distribution and social networks among traditional healers in Kongwa District Tanzania"
Malaria remains one of the chief causes of mortality among young children in sub-Saharan Africa. For many years it has been recognized that a large percentage of deaths among young children with life-threatening illnesses could be avoided through timely administration of low-cost treatments such as oral rehydration solution, antibiotics and antimalarial drugs. Research was conducted between July 1998 and January 1999 on the roles of the formal and non-formal health systems in the treatment of (and referral patterns for) malaria in the Kongwa District of Central Tanzania. Specific aims were to: a) Document the current roles of traditional healers, traditional midwives, shopowners, and community health workers in the management of people presenting with symptoms of malaria; b) Examine patterns of information flow and patient referral between practitioners; and to c) Identify potential interventions to promote early and appropriate treatment of malaria. Data were gathered using the techniques of semi-structured interviews, knowledge/social network questionnaires, and geographical information systems (GIS). Results lead to a few conclusions: a) Due to limited number of trained health workers and highly dispersed population, all categories of practitioners need to be involved in the effort to improve treatment of malaria in the community; b) Shopowners are especially important for efforts to improve treatment of mild malaria and decrease spread of drug resistance; and c) Traditional healers are especially important for efforts to improve treatment of severe malaria. A subset could be identified who might carry out early treatment in the community, possibly with drugs such as artesunate suppositories.
Laboratory Research: 1st Prize
Project Title: "Rapid Diagnosis of Systemic Bacterial Infections by Using PCR"
Management of febrile injection drug users is a major public health problem. Most are admitted to the hospital to "rule out" serious systemic infections such as endocarditis. To triage these patients more appropriately, we explored the feasibility of using PCR for raid diagnosis of systemic infections. We conducted a prospective study of 124 consecutive consenting febrile injection drug users who presented to the Johns Hopkins Hospital Emergency Department. Genomic DNA was purified from these individuals' who blood using QIAamp DNA purification kits. PCR was performed using primers specific for 16S rRNA, a ubiquitous, highly conserved bacterial gene. PCR results were compared to blood culture (the current gold standard), and both were compared to clinical diagnosis. Out of 120 patients with complete data, PCR detected 22 of 28 blood culture-positive individuals (sensitivity=79%) and several culture-negative individuals (specificty=66%). Among patients diagnosed with a bacterial infection, PCR detected 40 or 74 patients (sensitivity=54%), whereas blood culture detected 23 (sensitivity=31%). PCR-negative patients rarely had positive blood cultures (negative predictive value=91%). These results suggest that a PCR-based rapid assay for bacteremia is a feasible diagnostic tool. Further refinement of the assay to improve sensitivity may permit its use for ruling our non-infected patients in the Emergency Department. Also, rapid diagnosis and speciation of systemic bacterial infections could lead to better-targeted therapy.
Laboratory Research: 2nd Prize
Project Title: "RSV Infection Exacerbates Antigen-Induced Airway Eosinophilia in Mice," Liliana Moreno, Maryna Eichelberger, and Marsha Wills-Karp
Viral infections have been shown to exacerbate allergic airway responses in susceptible individuals. In order to determine the effects of coincident viral infection on the development of allergic responses in mice (A/J) previously determined to be susceptible to such responses, we sensitized mice with PBS or allergen (OVA) (10ug) two weeks prior to intranasal challenge with virus alone (106 PFU), virus + OVA (1.5 % solution, 50 ul PBS), OVA alone or PBS alone. At the peak of viral infection on day four, we measured airway reactivity (AHR) to i.v. acethyoline (50 ug/kg), conducted bronchoalveolar lavage (BAL), collected lymph nodes for enumeration of CD4, DC8, and B cells by flow cytometry, and lungs were taken for histology analysis. We found that ova-challenge induced significant increases in AHR, concomitant with increases in BAL eosinophils and lymphocytes when compared to PBS-controls. Viral infection alone induced significant elevations in BAL macrophages and lymphocytes, with no effect on eosinophils, and resulted in increasing in lymph node DC8 positive cells. Viral induced airway hyperreactivity, reduced antigen-induced elevations in mucus containing cells in the lungs, and Interleukin-13 levels in the murine airway. These studies indicate that viral infection coincident with allergen exposure exacerbates some parameters of the allergic response, but diminished others, in genetically susceptible mice. In summary, the interaction between RSV and antigen is complex, and more studies need to be done to elucidate the role of RSV as a risk factor in the development of the allergic response.
Laboratory Research: 3rd Prize
Project Title: "Evaluation of HIV-1 DNA Vaccine"
Growing evidences have indicated that HIV-specific cytotoxic T lymphocytes (CTL) are important host defenses that limit viral replication after infection. DNA vaccination represent a novel strategy for inducing potent CD8+ CTL responses in vivo. Expression of HIV-1 structural proteins such as Gag by DNA vectors has been hampered by the stringent requirement of co-expression with other viral components, such as Rev and RRE. Furthermore, even with Rev and RRE, expression of HIV-1 Gag, Pol, or Env is negligible in murine cells. These problems have limited our ability to address a key issue of how to generate effective CTL response to Gag using a model. To overcome this problem, we have constructed several novel DNA expression vectors for evaluation of HIV-1 Gag Protein expression in primate and mouse cells and for generating immune response in mice after DNA vaccination. The DNA vectors described in this study will help to systematically evaluate the means to maximize induction of CTL response against HIV-1 Gag in the murine and other animal systems.