Browsing by Subject "HIV Seropositivity"
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Item Open Access Bacterial vaginosis as a risk factor for high-grade cervical lesions and cancer in HIV-seropositive women.(Int J Gynaecol Obstet, 2011-09) Denslow, Sheri A; Westreich, Daniel J; Firnhaber, Cynthia; Michelow, Pam; Williams, Sophie; Smith, Jennifer SOBJECTIVE: To assess the effect of bacterial vaginosis (BV) on the risk of high-grade squamous intraepithelial lesions (HSIL) among HIV-seropositive women. METHODS: A hospital-based prospective cohort study of HIV-seropositive women was conducted in Johannesburg, South Africa from January 2005 to September 2009. Multivariate log-binomial and Poisson regressions were used to estimate prevalence and rate ratios, respectively. RESULTS: Among 1954 HIV-seropositive women, the baseline prevalence of HSIL was 17%. BV prevalence was high (54%) and showed no association with prevalence of HSIL (adjusted prevalence ratio, 1.12; 95% confidence intervals (CI), 0.92-1.35) nor with cervical lesion progression at follow-up visit (n=503) (adjusted rate ratio: 1.00; 95% CI, 0.65-1.53). CONCLUSION: Among HIV-seropositive women, BV was not associated with an increased risk of HSIL or cervical lesion progression.Item Open Access Blood pressure level impacts risk of death among HIV seropositive adults in Kenya: a retrospective analysis of electronic health records.(BMC Infect Dis, 2014-05-22) Bloomfield, Gerald S; Hogan, Joseph W; Keter, Alfred; Holland, Thomas L; Sang, Edwin; Kimaiyo, Sylvester; Velazquez, Eric JBACKGROUND: Mortality among people with human immunodeficiency virus (HIV) infection is increasingly due to non-communicable causes. This has been observed mostly in developed countries and the routine care of HIV infected individuals has now expanded to include attention to cardiovascular risk factors. Cardiovascular risk factors such as high blood pressure are often overlooked among HIV seropositive (+) individuals in sub-Saharan Africa. We aimed to determine the effect of blood pressure on mortality among HIV+ adults in Kenya. METHODS: We performed a retrospective analysis of electronic medical records of a large HIV treatment program in western Kenya between 2005 and 2010. All included individuals were HIV+. We excluded participants with AIDS, who were <16 or >80 years old, or had data out of acceptable ranges. Missing data for key covariates was addressed by inverse probability weighting. Primary outcome measures were crude mortality rate and mortality hazard ratio (HR) using Cox proportional hazards models adjusted for potential confounders including HIV stage. RESULTS: There were 49,475 (74% women) HIV+ individuals who met inclusion and exclusion criteria. Mortality rates for men and women were 3.8 and 1.8/100 person-years, respectively, and highest among those with the lowest blood pressures. Low blood pressure was associated with the highest mortality incidence rate (IR) (systolic <100 mmHg IR 5.2 [4.8-5.7]; diastolic <60 mmHg IR 9.2 [8.3-10.2]). Mortality rate among men with high systolic blood pressure without advanced HIV (3.0, 95% CI: 1.6-5.5) was higher than men with normal systolic blood pressure (1.1, 95% CI: 0.7-1.7). In weighted proportional hazards regression models, men without advanced HIV disease and systolic blood pressure ≥140 mmHg carried a higher mortality risk than normotensive men (HR: 2.39, 95% CI: 0.94-6.08). CONCLUSIONS: Although there has been little attention paid to high blood pressure among HIV+ Africans, we show that blood pressure level among HIV+ patients in Kenya is related to mortality. Low blood pressure carries the highest mortality risk. High systolic blood pressure is associated with mortality among patients whose disease is not advanced. Further investigation is needed into the cause of death for such patients.Item Open Access Cervical cancer precursors and hormonal contraceptive use in HIV-positive women: application of a causal model and semi-parametric estimation methods.(PLoS One, 2014) Leslie, Hannah H; Karasek, Deborah A; Harris, Laura F; Chang, Emily; Abdulrahim, Naila; Maloba, May; Huchko, Megan JOBJECTIVE: To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. BACKGROUND: Human immunodeficiency virus (HIV)-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. METHODS: We developed a causal model of the factors related to combined oral contraceptive (COC) use and cervical intraepithelial neoplasia 2 or greater (CIN2+) and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric methods: g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. RESULTS: We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7%) were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9%) increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. CONCLUSION: Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an increased prevalence of CIN2+ associated with COC, evidence is insufficient to conclude causality. Priority areas for future studies to better satisfy causal criteria are identified.Item Open Access Changes in HIV risk behavior and seroincidence among clients presenting for repeat HIV counseling and testing in Moshi, Tanzania.(AIDS Care, 2012) Fiorillo, Suzanne P; Landman, Keren Z; Tribble, Alison C; Mtalo, Antipas; Itemba, Dafrosa K; Ostermann, Jan; Thielman, Nathan M; Crump, John AWhile HIV counseling and testing (HCT) has been considered an HIV preventive measure in Africa, data are limited describing behavior changes following HCT. This study evaluated behavior changes and estimated HIV seroincidence rate among returning HCT clients. Repeat and one-time testing clients receiving HCT services in Moshi, Tanzania were identified. Information about sociodemographic characteristics, HIV-related behaviors and testing reasons were collected, along with HIV serostatus. Six thousand seven hundred and twenty-seven clients presented at least once for HCT; 1235 (18.4%) were HIV seropositive, median age was 29.7 years and 3712 (55.3%) were women. 1382 repeat and 4272 one-time testers were identified. Repeat testers were more likely to be male, older, married, or widowed, and testing because of unfaithful partner or new sexual partner. One-time testers were more likely to be students and testing due to illness. At second test, repeat testers were more likely to report that partners had received HIV testing, not have concurrent partners, not suspect partners have HIV, and have partners who did not have other partners. Clients who intended to change behaviors after the first test were more likely to report having changed behaviors by remaining abstinent (OR 2.58; p<0.0001) or using condoms (OR 2.00; p=0.006) at the second test. HIV seroincidence rate was 1.49 cases/100 person-years (PY). Clients presenting for repeat HCT reported some reduction of risky behavior and improved knowledge of sexual practices and HIV serostatus of their partners. Promoting behavior change through HCT should continue to be a focus of HIV prevention efforts in sub-Saharan Africa.Item Open Access Correlates of HIV testing among abused women in South Africa.(Violence Against Women, 2011-08) Adams, Julie L; Hansen, Nathan B; Fox, Ashley M; Taylor, Baishakhi B; van Rensburg, Madri Jansen; Mohlahlane, Rakgadi; Sikkema, Kathleen JGender-based violence increases a woman's risk for HIV but little is known about her decision to get tested. We interviewed 97 women seeking abuse-related services from a nongovernmental organization (NGO) in Johannesburg, South Africa. Forty-six women (47%) had been tested for HIV. Caring for children (odds ratio [OR] = 0.27, 95% confidence interval [CI] = [0.07, 1.00]) and conversing with partner about HIV (OR = 0.13, 95% CI = [0.02, 0.85]) decreased odds of testing. Stronger risk-reduction intentions (OR = 1.27, 95% CI = [1.01, 1.60]) and seeking help from police (OR = 5.51, 95% CI = [1.18, 25.76]) increased odds of testing. Providing safe access to integrated services and testing may increase testing in this population. Infection with HIV is highly prevalent in South Africa where an estimated 16.2% of adults between the ages of 15 and 49 have the virus. The necessary first step to stemming the spread of HIV and receiving life-saving treatment is learning one's HIV serostatus through testing. Many factors may contribute to someone's risk of HIV infection and many barriers may prevent testing. One factor that does both is gender-based violence.Item Open Access Depressive symptoms, substance use, and HIV-related high-risk behaviors among opioid-dependent individuals: results from the Clinical Trials Network.(Substance use & misuse, 2011-01) Pilowsky, Daniel J; Wu, Li-Tzy; Burchett, Bruce; Blazer, Dan G; Ling, WalterThe sample included 343 opioid-dependent adults enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-002). Opioid-dependent individuals were recruited from 12 sites across the United States from January 2001 to July 2002. We examined associations between depressive symptoms, co-occurring substance use (i.e., the use of substances other than opioids), and HIV-related sexual and injection risk behaviors. Data were collected using the Addiction Severity Index and the HIV Risk Behavior Scale, and analyzed using linear regression. Depressive symptoms were associated with an increased level of injection risk behaviors but were not associated with risky sexual behaviors. The co-occurring use of amphetamines also increased the likelihood of risky sexual behaviors. The study limitations and clinical implications are noted. The study was funded by the U.S. National Institute on Drug Abuse.Item Restricted Gender differences in the risk of HIV infection among persons reporting abstinence, monogamy, and multiple sexual partners in northern Tanzania.(PLoS One, 2008-08-27) Landman, Keren Z; Ostermann, Jan; Crump, John A; Mgonja, Anna; Mayhood, Meghan K; Itemba, Dafrosa K; Tribble, Alison C; Ndosi, Evaline M; Chu, Helen Y; Shao, John F; Bartlett, John A; Thielman, Nathan MBACKGROUND: Monogamy, together with abstinence, partner reduction, and condom use, is widely advocated as a key behavioral strategy to prevent HIV infection in sub-Saharan Africa. We examined the association between the number of sexual partners and the risk of HIV seropositivity among men and women presenting for HIV voluntary counseling and testing (VCT) in northern Tanzania. METHODOLOGY/ PRINCIPAL FINDINGS: Clients presenting for HIV VCT at a community-based AIDS service organization in Moshi, Tanzania were surveyed between November 2003 and December 2007. Data on sociodemographic characteristics, reasons for testing, sexual behaviors, and symptoms were collected. Men and women were categorized by number of lifetime sexual partners, and rates of seropositivity were reported by category. Factors associated with HIV seropositivity among monogamous males and females were identified by a multivariate logistic regression model. Of 6,549 clients, 3,607 (55%) were female, and the median age was 30 years (IQR 24-40). 939 (25%) females and 293 (10%) males (p<0.0001) were HIV seropositive. Among 1,244 (34%) monogamous females and 423 (14%) monogamous males, the risk of HIV infection was 19% and 4%, respectively (p<0.0001). The risk increased monotonically with additional partners up to 45% (p<0.001) and 15% (p<0.001) for women and men, respectively with 5 or more partners. In multivariate analysis, HIV seropositivity among monogamous women was most strongly associated with age (p<0.0001), lower education (p<0.004), and reporting a partner with other partners (p = 0.015). Only age was a significant risk factor for monogamous men (p = 0.0004). INTERPRETATION: Among women presenting for VCT, the number of partners is strongly associated with rates of seropositivity; however, even women reporting lifetime monogamy have a high risk for HIV infection. Partner reduction should be coupled with efforts to place tools in the hands of sexually active women to reduce their risk of contracting HIV.Item Open Access Histoplasmosis among hospitalized febrile patients in northern Tanzania.(Trans R Soc Trop Med Hyg, 2012-08) Lofgren, Sarah M; Kirsch, Emily J; Maro, Venance P; Morrissey, Anne B; Msuya, Levina J; Kinabo, Grace D; Saganda, Wilbrod; Diefenthal, Helmut C; Ramadhani, Habib O; Wheat, L Joseph; Crump, John AHistoplasmosis may be common in East Africa but the diagnosis is rarely confirmed. We report 9 (0.9%) cases of probable histoplasmosis retrospectively identified among 970 febrile inpatients studied in northern Tanzania. Median (range) age was 31 (6, 44) years, 6 (67%) were female, 6 (67%) HIV-infected; 7 (78%) were clinically diagnosed with tuberculosis or bacterial pneumonia. Histoplasmosis is an important cause of febrile illness in Tanzania but is rarely considered in the differential diagnosis. Increased clinician awareness and availability of reliable diagnostic tests may improve patient outcomes.Item Open Access HIV/AIDS-related institutional mistrust among multiethnic men who have sex with men: effects on HIV testing and risk behaviors.(Health Psychol, 2012-05) Hoyt, Michael A; Rubin, Lisa R; Nemeroff, Carol J; Lee, Joyce; Huebner, David M; Proeschold-Bell, Rae JeanOBJECTIVE: To investigate relationships between institutional mistrust (systematic discrimination, organizational suspicion, and conspiracy beliefs), HIV risk behaviors, and HIV testing in a multiethnic sample of men who have sex with men (MSM), and to test whether perceived susceptibility to HIV mediates these relationships for White and ethnic minority MSM. METHOD: Participants were 394 MSM residing in Central Arizona (M age = 37 years). Three dimensions of mistrust were examined, including organizational suspicion, conspiracy beliefs, and systematic discrimination. Assessments of sexual risk behavior, HIV testing, and perceived susceptibility to HIV were made at study entry (T1) and again 6 months later (T2). RESULTS: There were no main effects of institutional mistrust dimensions or ethnic minority status on T2 risk behavior, but the interaction of systematic discrimination and conspiracy beliefs with minority status was significant such that higher levels of systematic discrimination and more conspiracy beliefs were associated with increased risk only among ethnic minority MSM. Higher levels of systematic discrimination were significantly related to lower likelihood for HIV testing, and the interaction of organizational suspicion with minority status was significant such that greater levels of organizational suspicion were related to less likelihood of having been tested for HIV among ethnic minority MSM. Perceived susceptibility did not mediate these relationships. CONCLUSION: Findings suggest that it is important to look further into the differential effects of institutional mistrust across marginalized groups, including sexual and ethnic minorities. Aspects of mistrust should be addressed in HIV prevention and counseling efforts.Item Open Access HLA class II-Restricted CD8+ T cells in HIV-1 Virus Controllers.(Scientific reports, 2019-07-15) Nyanhete, Tinashe E; Frisbee, Alyse L; Bradley, Todd; Faison, William J; Robins, Elizabeth; Payne, Tamika; Freel, Stephanie A; Sawant, Sheetal; Weinhold, Kent J; Wiehe, Kevin; Haynes, Barton F; Ferrari, Guido; Li, Qi-Jing; Moody, M Anthony; Tomaras, Georgia DA paradigm shifting study demonstrated that induction of MHC class E and II-restricted CD8+ T cells was associated with the clearance of SIV infection in rhesus macaques. Another recent study highlighted the presence of HIV-1-specific class II-restricted CD8+ T cells in HIV-1 patients who naturally control infection (virus controllers; VCs). However, questions regarding class II-restricted CD8+ T cells ontogeny, distribution across different HIV-1 disease states and their role in viral control remain unclear. In this study, we investigated the distribution and anti-viral properties of HLA-DRB1*0701 and DQB1*0501 class II-restricted CD8+ T cells in different HIV-1 patient cohorts; and whether class II-restricted CD8+ T cells represent a unique T cell subset. We show that memory class II-restricted CD8+ T cell responses were more often detectable in VCs than in chronically infected patients, but not in healthy seronegative donors. We also demonstrate that VC CD8+ T cells inhibit virus replication in both a class I- and class II-dependent manner, and that in two VC patients the class II-restricted CD8+ T cells with an anti-viral gene signature expressed both CD4+ and CD8+ T cell lineage-specific genes. These data demonstrated that anti-viral memory class II-restricted CD8+ T cells with hybrid CD4+ and CD8+ features are present during natural HIV-1 infection.Item Open Access Perceived acceptability of home-based couples voluntary HIV counseling and testing in Northern Tanzania.(AIDS Care, 2012) Njau, B; Watt, MH; Ostermann, J; Manongi, R; Sikkema, KJIt is estimated that 5.6% of the Tanzanian population ages 15-49 are infected with HIV, but only 30% of adults have ever had an HIV test. Couples' testing has proven to increase testing coverage and introduce HIV prevention, but barriers include access to testing services and unequal gender dynamics in relationships. Innovative approaches are needed to address barriers to couple's testing and increase uptake of HIV testing. Using qualitative data collection methods, a formative study was conducted to assess the acceptability of a home-based couples counseling and testing (HBCCT) approach. Eligible study participants included married men and women, HIV-infected individuals, health care and home-based care providers, voluntary counseling and testing counselors, and community leaders. A total of 91 individuals participated in focus group discussions (FGDs) and in-depth interviews conducted between September 2009 and January 2010 in rural settings in Northern Tanzania. An HBCCT intervention appears to be broadly acceptable among participants. Benefits of HBCCT were identified in terms of access, confidentiality, and strengthening the relationship. Fears of negative consequences from knowing one's HIV status, including stigma, blame, physical abuse, or divorce, remain a concern and a potential barrier to the successful provision of the intervention. Lessons for implementation highlighted the importance of appointments for home visits, building relationships of confidence and trust between counselors and clients, and assessing and responding to a couple's readiness to undergo HIV testing. HBCCT should addresses HIV stigma, emphasize confidentiality, and improve communication skills for disclosure and decision-making among couples.Item Open Access Referring heroin users from compulsory detoxification centers to community methadone maintenance treatment: a comparison of three models.(BMC Public Health, 2013-08-13) Yan, Liping; Liu, Enwu; McGoogan, Jennifer M; Duan, Song; Wu, Li-Tzy; Comulada, Scott; Wu, ZunyouBACKGROUND: Both compulsory detoxification treatment and community-based methadone maintenance treatment (MMT) exist for heroin addicts in China. We aim to examine the effectiveness of three intervention models for referring heroin addicts released from compulsory detoxification centers to community methadone maintenance treatment (MMT) clinics in Dehong prefecture, Yunnan province, China. METHODS: Using a quasi-experimental study design, three different referral models were assigned to four detoxification centers. Heroin addicts were enrolled based on their fulfillment to eligibility criteria and provision of informed consent. Two months prior to their release, information on demographic characteristics, history of heroin use, and prior participation in intervention programs was collected via a survey, and blood samples were obtained for HIV testing. All subjects were followed for six months after release from detoxification centers. Multi-level logistic regression analysis was used to examine factors predicting successful referrals to MMT clinics. RESULTS: Of the 226 participants who were released and followed, 9.7% were successfully referred to MMT(16.2% of HIV-positive participants and 7.0% of HIV-negative participants). A higher proportion of successful referrals was observed among participants who received both referral cards and MMT treatment while still in detoxification centers (25.8%) as compared to those who received both referral cards and police-assisted MMT enrollment (5.4%) and those who received referral cards only (0%). Furthermore, those who received referral cards and MMT treatment while still in detoxification had increased odds of successful referral to an MMT clinic (adjusted OR = 1.2, CI = 1.1-1.3). Having participated in an MMT program prior to detention (OR = 1.5, CI = 1.3-1.6) was the only baseline covariate associated with increased odds of successful referral. CONCLUSION: Findings suggest that providing MMT within detoxification centers promotes successful referral of heroin addicts to community-based MMT upon their release.Item Open Access Systematic review of the performance of HIV viral load technologies on plasma samples.(PLoS One, 2014) Sollis, Kimberly A; Smit, Pieter W; Fiscus, Susan; Ford, Nathan; Vitoria, Marco; Essajee, Shaffiq; Barnett, David; Cheng, Ben; Crowe, Suzanne M; Denny, Thomas; Landay, Alan; Stevens, Wendy; Habiyambere, Vincent; Perrins, Jos; Peeling, Rosanna WBACKGROUND: Viral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring. METHODS AND FINDINGS: A search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n = 25), Cobas TaqMan v2.0 (n = 11), Abbott RealTime HIV-1 (n = 23), Versant HIV-1 RNA bDNA 3.0 (n = 15), Versant HIV-1 RNA kPCR 1.0 (n = 2), ExaVir Load v3 (n = 2), and NucliSens EasyQ v2.0 (n = 1). All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2-26% and 9-70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0-5.1%) and 5.44% (range 1.17-30.00%) across the range of VL counts (2log10-7log10). CONCLUSIONS: This review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same technology platform to ensure appropriate interpretation of changes in VL. Prospero registration # CD42013003603.Item Open Access The development and psychometric properties of the HIV and Abuse Related Shame Inventory (HARSI).(AIDS Behav, 2012-05) Neufeld, Sharon AS; Sikkema, Kathleen J; Lee, Rachel S; Kochman, Arlene; Hansen, Nathan BShame has been shown to predict sexual HIV transmission risk behavior, medication non-adherence, symptomatic HIV or AIDS, and symptoms of depression and PTSD. However, there remains a dearth of tools to measure the specific constructs of HIV-related and sexual abuse-related shame. To ameliorate this gap, we present a 31-item measure that assesses HIV and sexual abuse-related shame, and the impact of shame on HIV-related health behaviors. A diverse sample of 271 HIV-positive men and women who were sexually abused as children completed the HIV and Abuse Related Shame Inventory (HARSI) among other measures. An exploratory factor analysis supported the retention of three-factors, explaining 56.7% of the sample variance. These internally consistent factors showed good test-retest reliability, and sound convergent and divergent validity using eight well-established HIV specific and general psychosocial criterion measures. Unlike stigma or discrimination, shame is potentially alterable through individually-focused interventions, making the measurement of shame clinically meaningful.Item Open Access The impact of structured support groups for pregnant South African women recently diagnosed HIV positive.(Women Health, 2011-08-31) Mundell, Jonathan P; Visser, Maretha J; Makin, Jennifer D; Kershaw, Trace S; Forsyth, Brian WC; Jeffery, Bridget; Sikkema, Kathleen JThe authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women. Participants were expected to display increases in HIV disclosure, self-esteem, active coping and positive social support, and decreases in depression, avoidant coping, and negative social support. Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006. Using a quasi-experimental design, assessments were conducted at baseline and two and eight months post-intervention. A series of random effects regression analyses were conducted, with the three assessment points treated as a random effect of time. At both follow-ups, the rate of disclosure in the intervention group was significantly higher than that of the comparison group (p<0.001). Compared to the comparison group at the first follow-up, the intervention group displayed higher levels of active coping (t=2.68, p<0.05) and lower levels of avoidant coping (t=-2.02, p<0.05), and those who attended at least half of the intervention sessions exhibited improved self-esteem (t=2.11, p<0.05). Group interventions tailored for newly HIV positive pregnant women, implemented in resource-limited settings, may accelerate the process of adjusting to one's HIV status, but may not have sustainable benefits over time.Item Open Access WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study.(BMJ, 2010-03-30) Nadjm, Behzad; Amos, Ben; Mtove, George; Ostermann, Jan; Chonya, Semkini; Wangai, Hannah; Kimera, Juma; Msuya, Walii; Mtei, Frank; Dekker, Denise; Malahiyo, Rajabu; Olomi, Raimos; Crump, John A; Whitty, Christopher JM; Reyburn, HughOBJECTIVES: To assess the performance of WHO's "Guidelines for care at the first-referral level in developing countries" in an area of intense malaria transmission and identify bacterial infections in children with and without malaria. DESIGN: Prospective study. SETTING: District hospital in Muheza, northeast Tanzania. PARTICIPANTS: Children aged 2 months to 13 years admitted to hospital for febrile illness. MAIN OUTCOME MEASURES: Sensitivity and specificity of WHO guidelines in diagnosing invasive bacterial disease; susceptibility of isolated organisms to recommended antimicrobials. RESULTS: Over one year, 3639 children were enrolled and 184 (5.1%) died; 2195 (60.3%) were blood slide positive for Plasmodium falciparum, 341 (9.4%) had invasive bacterial disease, and 142 (3.9%) were seropositive for HIV. The prevalence of invasive bacterial disease was lower in slide positive children (100/2195, 4.6%) than in slide negative children (241/1444, 16.7%). Non-typhi Salmonella was the most frequently isolated organism (52/100 (52%) of organisms in slide positive children and 108/241 (45%) in slide negative children). Mortality among children with invasive bacterial disease was significantly higher (58/341, 17%) than in children without invasive bacterial disease (126/3298, 3.8%) (P<0.001), and this was true regardless of the presence of P falciparum parasitaemia. The sensitivity and specificity of WHO criteria in identifying invasive bacterial disease in slide positive children were 60.0% (95% confidence interval 58.0% to 62.1%) and 53.5% (51.4% to 55.6%), compared with 70.5% (68.2% to 72.9%) and 48.1% (45.6% to 50.7%) in slide negative children. In children with WHO criteria for invasive bacterial disease, only 99/211(47%) of isolated organisms were susceptible to the first recommended antimicrobial agent. CONCLUSIONS: In an area exposed to high transmission of malaria, current WHO guidelines failed to identify almost a third of children with invasive bacterial disease, and more than half of the organisms isolated were not susceptible to currently recommended antimicrobials. Improved diagnosis and treatment of invasive bacterial disease are needed to reduce childhood mortality.