Elijah Paintsil

Survival of Hepatitis C Virus in Syringes: Implication for Transmission among Injection Drug Users

BACKGROUND We hypothesized that the high prevalence of hepatitis C virus (HCV) among injection drug users might be due to prolonged virus survival in contaminated syringes. METHODS We developed a microculture assay to examine the viability of HCV. Syringes were loaded with blood spiked with HCV reporter virus (Jc1/GLuc2A) to simulate 2 scenarios of residual volumes: low void volume (2 microL) for 1-mL insulin syringes and high void volume (32 microL) for 1-mL tuberculin syringes. Syringes were stored at 4 degrees C, 22 degrees C, and 37 degrees C for up to 63 days before testing for HCV infectivity by using luciferase activity. RESULTS The virus decay rate was biphasic (t1/2alpha= 0.4 h and t1/2beta = 28 hh). Insulin syringes failed to yield viable HCV beyond day 1 at all storage temperatures except 4 degrees , in which 5% of syringes yielded viable virus on day 7. Tuberculin syringes yielded viable virus from 96%, 71%, and 52% of syringes after storage at 4 degrees, 22 degrees, and 37 degrees for 7 days, respectively, and yielded viable virus up to day 63. CONCLUSIONS The high prevalence of HCV among injection drug users may be partly due to the resilience of the virus and the syringe type. Our findings may be used to guide prevention strategies.

Competitive Fitness of Nevirapine-Resistant Human Immunodeficiency Virus Type 1 Mutants

ABSTRACT Determining the fitness of drug-resistant human immunodeficiency virus type 1 (HIV-1) strains is necessary for the development of population-based studies of resistance patterns. For this purpose, we have developed a reproducible, systematic assay to determine the competitive fitness of HIV-1 drug-resistant mutants. To demonstrate the applicability of this assay, we tested the fitness of the five most common nevirapine-resistant mutants (103N, 106A, 181C, 188C, and 190A), with mutations in HIV-1 reverse transcriptase (RT), singly and in combination (for a total of 31 variants) in a defined HIV-1 background. For these experiments, the 27 RT variants that produced viable virus were cocultured with wild-type virus without nevirapine. The ratios of the viral species were determined over time by utilization of a quantitative real-time RT-PCR-based assay. These experiments revealed that all of the viable variants were less fit than the wild type and demonstrated that the order of relative fitness of the single mutants tested was as follows: 103N > 181C > 190A > 188C > 106A. This order correlated with the commonality of these mutants as a result of nevirapine monotherapy. These investigations also revealed that, on average, the double mutants were less fit than the single mutants and the triple mutants were less fit than the double mutants. However, the fitness of the single and double mutants was often not predictive of the fitness of the derivative triple mutants, suggesting the presence of complex interactions between the closely aligned residues that confer nevirapine resistance. This complexity was also evident from the observation that all three of the replication-competent quadruple mutants were fitter than most of the triple mutants, and in some cases, even the double mutants. Our data suggest that, in many cases, viral fitness is the determining factor in the evolution of nevirapine-resistant mutants in vivo, that interactions between the residues that confer nevirapine resistance are complex, and that these interactions substantially affect reverse transcriptase structure and/or function.

Update on successes and challenges regarding mother-to-child transmission of HIV.

Purpose of review There is an unprecedented global commitment to reverse the pediatric HIV epidemic by making prevention of mother-to-child transmission (PMTCT) services accessible in all countries. This review outlines the successes made and the challenges that remain. Recent findings In resource-rich countries, mother-to-child transmission rates of HIV as low as 1% have been achieved. The efficacy of short-course antiretrovirals for PMTCT in Africa is estimated at 50%. Coinfections with herpes simplex virus type 2, other sexually transmitted infections resulting in genital ulcers, and endemic infectious diseases (e.g., malaria) may increase the risk of mother-to-child transmission of HIV. Vertical transmission of drug-resistant viruses has been reported; the prevalence and effect of transmitted resistant virus on treatment outcomes are under investigation. Obstacles facing PMTCT in resource-limited countries include the lack of healthcare infrastructure, limited manpower, and competing public health priorities with the limited healthcare budget. Summary Although the birth of an HIV-infected child in a resource-rich country is now a sentinel health event, in most resource-limited countries the birth of an HIV-infected child continues to be the status quo. Comprehensive PMTCT, including antiretroviral treatment for HIV-infected women and children, should be paramount in resource-limited countries.

Hepatitis C Virus Maintains Infectivity for Weeks after Drying on Inanimate Surfaces at Room Temperature: Implications for Risks of Transmission

BACKGROUND Healthcare workers may come into contact with fomites that contain infectious hepatitis C virus (HCV) during preparation of plasma or following placement or removal of venous lines. Similarly, injection drugs users may come into contact with fomites. Hypothesizing that prolonged viability of HCV in fomites may contribute significantly to incidence, we determined the longevity of virus infectivity and the effectiveness of antiseptics. METHODS We determined the volume of drops misplaced during transfer of serum or plasma. Aliquots equivalent to the maximum drop volume of plasma spiked with the 2a HCV reporter virus were loaded into 24-well plates. Plates were stored uncovered at 3 temperatures: 4°C, 22°C, and 37°C for up to 6 weeks before viral infectivity was determined in a microculture assay. RESULTS The mean volume of an accidental drop was 29 µL (min-max of 20-33 µL). At storage temperatures 4°C and 22°C, we recovered viable HCV from the low-titer spots for up to 6 weeks of storage. The rank order of HCV virucidal activity of commonly used antiseptics was bleach (1:10) > cavicide (1:10) > ethanol (70%). CONCLUSIONS The hypothesis of potential transmission from fomites was supported by the experimental results. The anti-HCV activity of commercial antiseptics varied.

Hepatitis C virus infection among drug injectors in St Petersburg, Russia: social and molecular epidemiology of an endemic infection

AIMS To understand the epidemiology and transmission patterns of hepatitis C virus (HCV), the predominant blood borne-pathogen infecting injection drug users (IDUs), in a part of the former Soviet Union. DESIGN Cross-sectional respondent-driven sample of IDUs. SETTING St Petersburg, Russia. PARTICIPANTS A total of 387 IDUs were recruited in late 2005 and throughout 2006. MEASUREMENTS Participants were surveyed to collect demographic, medical and both general and dyad-specific drug injection and sexual behaviors. A blood sample was collected to detect antibodies to hepatitis C and to amplify viral RNA for molecular analysis. The molecular data, including genotypes, were analyzed spatially and linkage patterns were compared to the social linkages obtained by respondent-driven sampling (RDS) for chains of respondents and among the injection dyads. FINDINGS HCV infection was all but ubiquitous: 94.6% of IDUs were HCV-seropositive. Among the 209 viral sequences amplified, genotype 3a predominated (n = 119, 56.9%), followed by 1b (n = 61, 29.2%) and 1a (n = 25, 11.9%). There was no significant clustering of genotypes spatially. Neither genotypes nor closely related sequences were clustered within RDS chains. Analysis of HCV sequences from dyads failed to find associations of genotype or sequence homology within pairs. CONCLUSIONS Genotyping reveals that there have been at least five unique introductions of HCV genotypes into the IDU community in St Petersburg. Analysis of prevalent infections does not appear to correlate with the social networks of IDUs, suggesting that simple approaches to link these networks to prevalent infections, rather than incident transmission, will not prove meaningful. On a more positive note, the majority of IDUs are infected with 3a genotype that is associated with sustained virological response to antiviral therapy.

Longitudinal association of alcohol use with HIV disease progression and psychological health of women with HIV

Abstract We evaluated the association of alcohol consumption and depression, and their effects on HIV disease progression among women with HIV. The study included 871 women with HIV who were recruited from 1993–1995 in four US cities. The participants had physical examination, medical record extraction, and venipuncture, CD4+T-cell counts determination, measurement of depression symptoms (using the self-report Center for Epidemiological Studies-Depression Scale), and alcohol use assessment at enrollment, and semiannually until March 2000. Multilevel random coefficient ordinal models as well as multilevel models with joint responses were used in the analysis. There was no significant association between level of alcohol use and CD4+ T-cell counts. When participants were stratified by antiretroviral therapy (ART) use, the association between alcohol and CD4+ T-cell did not reach statistical significance. The association between alcohol consumption and depression was significant (p<0.001). Depression had a significant negative effect on CD4+ T-cell counts over time regardless of ART use. Our findings suggest that alcohol consumption has a direct association with depression. Moreover, depression is associated with HIV disease progression. Our findings have implications for the provision of alcohol use interventions and psychological resources to improve the health of women with HIV.

Alcohol Abuse, Sexual Risk Behaviors and Sexually Transmitted Infections in Women in Moshi Urban District, Northern Tanzania

Background: To assess the covariates of alcohol abuse and the association between alcohol abuse, high-risk sexual behaviors and sexually transmitted infections (STIs). Methods: Two thousand and nineteen women aged 20 to 44 were randomly selected in a 2-stage sampling from the Moshi urban district of northern Tanzania. Participant’s demographic and socio-economic characteristics, alcohol use, sexual behaviors, and STIs were assessed. Blood and urine samples were drawn for testing of human immunodeficiency virus, herpes simplex virus, syphilis, chlamydia, gonorrhea, trichomonas, and mycoplasma genitalium infections. Results: Adjusted analyses showed that a history of physical (OR = 2.05; 95% CI: 1.06–3.98) and sexual violence (OR = 1.63; 95% CI: 1.05–2.51) was associated with alcohol abuse. Moreover, alcohol abuse was associated with number of sexual partners (OR = 1.66; 95% CI: 1.01–2.73). Women who abused alcohol were more likely to report STIs symptoms (OR = 1.61; 95% CI: 1.08–2.40). Women who had multiple sexual partners were more likely to have an STI (OR = 2.41; 95% CI: 1.46–4.00) compared to women with 1 sexual partner. There was no direct association between alcohol abuse and prevalence of STIs (OR = 0.86; 95% CI: 0.55–1.34). However, alcohol abuse was indirectly associated with STIs through its association with multiple sexual partners. Conclusions: The findings of alcohol abuse among physically and sexually violated women as well as the association between alcohol abuse and a history of symptoms of STIs and testing positive for STIs have significant public health implications. In sub-Saharan Africa, where women are disproportionately affected by the HIV epidemic screening for alcohol use should be part of comprehensive STIs and HIV prevention programs.

Update on recent guidelines for the management of urinary tract infections in children: the shifting paradigm.

Purpose of review Recent guidelines on the management of urinary tract infections (UTIs) in children have seen a shift from aggressive imaging studies and the use of prophylactic antibiotics to a more restrictive and targeted approach. This review focuses on new additions to the literature on management of UTI from January 2011 to September 2012. Recent findings The causal relationship between UTI–vesicoureteral reflux (VUR) and renal scarring has been challenged by several studies. Concerns about unnecessary exposure to ionizing radiation, invasiveness of some of the procedures, and risk of infection have also been raised. With improved prenatal ultrasound, a ‘top-down’ approach to investigating febrile UTI in children using renal bladder ultrasound alone as an initial study has become popular. Several studies have reported that prophylactic antibiotics and imaging studies after first UTI can be reduced substantially without affecting the risk of recurrent UTI or renal scarring. Summary The use of targeted imaging approach in evaluating febrile UTI in children may lead to improved resource use and reduction of potential harmful procedures and interventions, without affecting outcomes of UTI in children. Providers using current guidelines should endeavor to collect practice-based evidence to validate and inform future guidelines.

Association of age at first sex with HIV-1 HSV-2 and other sexual transmitted infections among women in northern Tanzania.

Background: To examine the association between age at first sex and the prevalence of sexually transmitted infections (STIs), including HIV-1 and HSV-2, in women in Moshi urban district, northern Tanzania. Methods: A total of 2019 women aged 20 to 44 were randomly selected in a 2-stage sampling from Moshi urban district, northern Tanzania. Information on demographics and sexual behaviors were obtained. Blood and urine samples were drawn for testing of HIV-1, HSV-2, and other STIs. Results: Women who had their first sexual intercourse at age between 18 and 19 (OR = 0.66; 95% CI = 0.50–0.86) or 20+ (OR = 0.46; 95% CI = 0.36–0.60) were less likely to have STIs, including HIV-1 and HSV-2, than women who had their first intercourse before their 18th birthday. The hazards of having had first sex at an earlier age were significantly higher for women who tested positive for STIs (HR = 1.52; 95% CI: 1.37–1.69) or had STI symptoms (HR = 1.17; 95% CI: 1.05–1.30). Early age at first sex was associated with having a regular noncohabiting partner (HR = 1.40; 95% CI: 1.23–1.58), female circumcision (HR = 1.20; 95% CI: 1.02–1.40), and coercion at first intercourse (HR = 1.47; 95% CI: 1.15–1.89). Conclusions: In sub-Saharan Africa, where the prevalence of HIV and other STIs is high, a better understanding of the determinants of the age at first sex is crucial for HIV/STI prevention programs. Prevention programs should not only aim at delaying the age at first sex but also address factors leading to early age at first sex.

Pediatric community-acquired methicillin-resistant Staphylococcus aureus infection and colonization: trends and management.

Purpose of review The scourge of community-acquired methicillin-resistant Staphylococcus aureus in pediatrics continues unabated. This review provides information on changes in epidemiology, therapeutic considerations, and measures to control the epidemic. Recent findings The epidemiology and clinical manifestations of methicillin-resistant S. aureus have undergone important changes that pose challenges in recognition, diagnosis, and treatment for the pediatrician. Community-acquired methicillin-resistant S. aureus used to be predominantly associated with localized disease among previously healthy children; however, there are recent reports of more invasive and severe diseases with some fatalities. The antibiotic susceptibility pattern is also changing with some community-acquired methicillin-resistant S. aureus having resistance patterns indistinguishable from that of hospital-acquired methicillin-resistant S. aureus. Thus the choice of antibiotics is becoming even more challenging in pediatrics, with an already-limited armamentarium of antibiotics. The management of common skin diseases such as furunculosis and boils now requires close collaboration between the general pediatrician and the infectious diseases specialist. Summary As the burden of community-acquired methicillin-resistant S. aureus disease continues to increase, pediatricians must have a high index of suspicion and must institute appropriate antimicrobial therapy based on community or regional antibiotic susceptibility of community-acquired methicillin-resistant S. aureus. There is an urgent need for effective infection control programs, including active surveillance components, to help curb the epidemic.