Global research priorities for infections that affect the nervous system.

Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries.

Mortality in hospitalized patients with tuberculous meningitis.

BACKGROUND: To evaluate the mortality in hospitalized patients with tuberculous meningitis and describe factors associated with an increased risk of mortality. METHODS: Retrospective study of hospitalized patients with tuberculous meningitis between 2006 and 2015 in Peru performing a generalized linear regression to identify factors predictive of in-hospital mortality. RESULTS: Of 263 patients, the median age was 35 years, 72.6% were men, 38% were positive for HIV upon admission, 24% had prior TB infections and 2.3% had prior MDR-TB infections. In-hospital mortality was 30.4% of all study patients with a final diagnosis of TBM. When multivariable analysis was applied, significant associations with in-hospital mortality were seen among patients with HIV (RR 2.06; Confidence Interval 95% (95% CI) 1.44-2.94), BMRC II (RR 1.78; 95% CI 1.07-2.97), BMRC III (RR 3.11; 95% CI 1.78-5.45) and positive CSF cultures (RR 1.95; 95% CI 1.39-2.74). CONCLUSIONS: In-hospital mortality is higher among patients with HIV infections, age over 40 years, positive CSF TB culture and BMRC stage II or III.

Body Parts Matter: Social, Behavioral, and Biological Considerations for Urethral, Pharyngeal, and Rectal Gonorrhea and Chlamydia Screening Among MSM in Lima, Peru.

BACKGROUND: Gonorrhea (Neisseria gonorrhoeae [GC]) and chlamydia (Chlamydia trachomatis [CT]) disproportionately affect men who have sex with men (MSM), and public health implications vary by anatomic site and bacterial agent. Urethral and rectal GC and CT can increase risk of HIV transmission, whereas pharyngeal GC may be a reservoir for antimicrobial resistance. To define screening priorities in Latin America, we compare differences in the prevalence and correlates of urethral, pharyngeal, and rectal GC and CT among MSM in Peru. METHODS: A cross-sectional sample of 787 MSM from Lima was screened between 2012 and 2014. We described prevalence of urethral, pharyngeal, and rectal GC and CT infection and conducted bivariate analyses of associations with social, behavioral, and biological characteristics. Poisson regression analyses assessed the correlates of each infection at each anatomic site. RESULTS: The most commonly symptomatic infection (urethral GC; 42.1%) was the least prevalent (2.4%). The most prevalent infections were rectal CT (15.8%) and pharyngeal GC (9.9%). Rectal CT was the least commonly symptomatic (2.4%) infection, and was associated with younger age (adjusted prevalence ratio [95% confidence interval], 0.96 [0.94-0.98]), HIV infection (1.46 [1.06-2.02]), and pasivo (receptive; 3.59 [1.62-7.95]) and moderno (versatile; 2.63 [1.23-5.60]) sexual roles. CONCLUSIONS: Results highlight limitations of current syndromic screening strategies for sexually transmitted diseases in Peru, wherein urethral CT and rectal GC and CT may be missed due to their frequently asymptomatic presentations. Successful management of GC and CT infections among MSM in low-resource settings requires differentiating between bacterial agent, symptomatic presentation, associated risk factors, and public health implications of untreated infection at different anatomic sites.

Expedited Partner Therapy (EPT) increases the frequency of partner notification among MSM in Lima, Peru: a pilot randomized controlled trial.

BACKGROUND: Expedited Partner Therapy (EPT) has been shown to improve treatment outcomes among heterosexual partners of individuals with curable sexually transmitted infections (STIs). Although the use of EPT with men who have sex with men (MSM) has been debated, due to the potential for missed opportunities to diagnose unidentified cases of HIV and syphilis infection in symptomatic partners, increases in partner notification (PN) resulting from use of EPT may promote testing and treatment of otherwise unidentified partners. We assessed the impact of EPT on self-reported PN among MSM in Peru with gonorrheal (GC) and/or chlamydial (CT) infection. METHODS: We enrolled 173 MSM in Lima, Peru with symptomatic or asymptomatic GC and/or CT infection between 2012 and 2014. We enrolled 44 MSM with symptomatic urethritis/proctitis and 129 MSM with asymptomatic GC/CT infection, diagnosed based on nucleic acid testing (Aptima Combo 2 Transcription-Mediated Amplification [TMA]) from urethral, pharyngeal, and rectal sites. Eligible participants were randomly assigned to receive either standard PN counseling (n = 84) or counseling plus EPT (cefixime 400 mg/azithromycin 1 g) for up to five recent partners (n = 89). Self-reported notification was assessed by computer-assisted self-administered survey among 155 participants who returned for 14-day follow-up. RESULTS: The median age of participants was 26 (interquartile range [IQR]: 23-31) with a median of 3 sexual partners (IQR: 2-4) in the previous 30-day period. Among all participants, 111/155 (71.6%) notified at least one partner at 14-day follow-up with a median of 1 partner notified per participant (IQR: 0-2). For participants randomized to receive EPT, 69/83 (83.1%) reported notifying at least one partner, compared with 42/72 (58.3%) of participants in the control arm (odds ratio = 3.52; 95% confidence interval [CI]: 1.68-7.39). The proportion of all recent partners notified was significantly greater in the EPT than in the control arm (53.5%, 95% CI: 45.0-62.0% versus 36.4%, 95% CI: 27.0-47.4%). CONCLUSIONS: Provision of EPT led to significant increases in notification among Peruvian MSM diagnosed with GC/CT infection. Additional research is needed to assess the impact of EPT on biological outcomes, including persistent or recurrent infection, antimicrobial resistance, and HIV/STI transmission, in MSM sexual networks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01720654 . Registered on 10/29/2012.

A community-based cluster randomized survey of noncommunicable disease and risk factors in a peri-urban shantytown in Lima, Peru.

BACKGROUND: An estimated 863 million people-a third of the world's urban population-live in slums, yet there is little information on the disease burden in these settings, particularly regarding chronic preventable diseases. METHODS: From March to May 2012, we conducted a cluster randomized survey to estimate the prevalence of noncommunicable diseases (NCDs) and associated risk factors in a peri-urban shantytown north of Lima, Peru. Field workers administered a questionnaire that included items from the WHO World Health Survey and the WHO STEPS survey of chronic disease risk factors. We used logistic regression to assess the associations of NCDs and related risk factors with age and gender. We accounted for sampling weights and the clustered sampling design using statistical survey methods. RESULTS: A total of 142 adults were surveyed and had a weighted mean age of 36 years (range 18-81). The most prevalent diseases were depression (12%) and chronic respiratory disease (8%), while lifetime prevalence of cancer, arthritis, myocardial infarction, and diabetes were all less than 5%. Fifteen percent of respondents were hypertensive and the majority (67%) was unaware of their condition. Being overweight or obese was common for both genders (53%), but abdominal obesity was more prevalent in women (54% vs. 10% in men, p < 0.001). Thirty-five percent of men binge drank and 34% reported current smoking; these behaviors were less common among women (4% binge drank, p < 0.001; 8% smoked, p = 0.002). Increasing age was associated with an increased risk of abdominal obesity (Odds Ratio (OR) = 1.04, 95% CI = 1.01, 1.07, p = 0.02), hypertension (OR = 1.06, 95% CI = 1.02, 1.10, p = 0.006), arthritis (OR = 1.07, 95% CI = 1.03, 1.11, p < 0.001) and cancer (OR = 1.13, 95% CI = 1.07, 1.20, p < 0.001) in adjusted models. The prevalences of other NCDs and related risk factors were similar when stratified by age or gender. CONCLUSIONS: This study underlines the important burden of noncommunicable disease in informal settlements in Peru and suggests that prevention and treatment interventions could be optimized according to age and gender.

In Peru, reporting male sex partners imparts significant risk of incident HIV/sexually transmitted infection: all men Engaging in same-sex behavior need prevention services.

BACKGROUND: Detailed information on the sexual behavior of bisexual, non-gay-identified men and the relationship between same-sex behavior and HIV/sexually transmitted infection (STI) incidence is limited. This study provides information on the sexual behavior with male partners of non-gay-identified men in urban, coastal Peru and the relationship of this behavior with HIV/STI incidence. METHODS: We analyzed data from 2146 non-gay-identified men with a baseline and then 2 years of annual follow-up, including detailed information on sexual behavior with up to 5 sex partners, to determine the characteristics associated with bisexual behavior. Discrete time proportional hazards models were used to determine the effect of self-reported sex with men on subsequent HIV/STI incidence. RESULTS: Over the 3 study visits, sex with a man was reported by 18.9% of men, 90% of whom also reported sex with a female partner. At baseline, reported bisexual behavior was associated with other sexual risk behaviors such as exchanging sex for money and increased risk of HIV, herpes simplex virus type 2, and gonorrhea. The number of study visits in which recent sex with men was reported was positively correlated with risk of other sexual risk behaviors and incident HIV, herpes simplex virus type 2, and gonorrhea. Recent sex with a man was associated with increased HIV/STI incidence (hazard ratio, 1.79; confidence interval, 1.19-2.70), after adjusting for sociodemographics and other sexual risk behaviors. CONCLUSIONS: Given the prevalence of recent sex with men and the relationship of this behavior with HIV/STI incidence, interventions with non-gay-identified men who have sex with men and their partners are warranted.

Prevalence and predictors of cervicitis in female sex workers in Peru: an observational study.

BACKGROUND: Cervicitis is a syndrome of cervical inflammation and a common condition in female sex workers (FSW), a subpopulation vulnerable to sexually transmitted infections. Local data is essential for guiding syndromic management of cervicitis in FSW working in Peru. We sought to describe the prevalence and etiologies of cervicitis in this population. We also aimed to identify sociodemographic, behavioral and biological factors associated with cervicitis, including bacterial vaginosis (BV), a condition with a possible role in cervicitis. METHODS: FSW 18 years of age or older presenting to a free public sexual health clinic in Callao-Lima, Peru were eligible for inclusion upon consent. 467 participants completed a face-to-face questionnaire and underwent genital examination. Vaginal, endocervical and blood samples were collected and tested for C. trachomatis (CT), N. gonorrhea (GC), T. vaginalis (TV), BV, HIV and Human T-Cell Lymphotropic Virus -1. Logistic regression was used to determine whether sociodemographic, behavioral, or other sexual health related characteristics were associated with the diagnosis of cervicitis. RESULTS: Cervicitis was detected in 99 (24.9%) of 397 FSW. The presence of cervicitis was unable to be determined in 70 participants. In women with cervicitis, CT was present in 4.6% (4/87), TV in 4.0% (4/99), GC in 0% (0/87) and no pathogen was detected on cervical microbiology in 91.9% (91/99). BV was detected on vaginal microbiology in 36.9% (31/84) of cervicitis cases. BV was more common in women with cervicitis, however this association did not reach statistical significance (aOR = 1.47 [0.87, 2.48], p = 0.15). Other STI were not associated with cervicitis. Regular clinic attendance (aOR = 0.54 [0.34, 0.87], p = 0.01) and Ecuadorian nationality (aOR = 0.31 [0.13, 0.76], p = 0.01) were associated with reduced risk of cervicitis. CONCLUSIONS: Cervicitis was common in FSW working Peru and was predominantly nongonococcal and non-chlamydial in etiology. Further study is warranted to clarify the role of BV and other emerging cervicitis pathogens in this population. The current Peruvian program of free health checks for FSW may be effective for reducing rates of cervicitis. The protective effect of Ecuadorian nationality prompts further study.

A cross-sectional study of knowledge of sex partner serostatus among high-risk Peruvian men who have sex with men and transgender women: implications for HIV prevention.

BACKGROUND: Knowledge of a sex partner's HIV serostatus can influence sexual behavior and inform harm-reduction strategies. We sought to determine how often Peruvian men who have sex with men (MSM) and transgender women (TW) knew the HIV serostatus of their sex partners, if this knowledge was associated with any predictive factors or unprotected anal intercourse (UAI), and if UAI was associated with partner serostatus. METHODS: We analyzed data from the 2008 Peruvian MSM Sentinel Surveillance Survey. Data were collected by CASI about each participant's three most recent male sex partners. Primary outcome was knowledge of a partner's HIV test result. Multivariate analysis assessed the effect of age, education, sexual identity, number of male partners, alcohol use during intercourse, type of partnership and length of partnership using logistic regression. RESULTS: 735 participants provided data on 1,643 of their most recent sex partners from the last 3 months. 179/735 (24.4%) of all participants knew HIV test results for at least one of their 3 most recent partners, corresponding to 230/1643 (14.0%) of all sexual partnerships in the last 3 months. In multivariate analysis, casual (OR: 0.27, 95% CI: 0.17-0.42) and exchange sex (OR: 0.31, 95% CI: 0.11-0.88) partners, compared to stable partners, were negatively associated with knowledge of partner serostatus, whereas relationships lasting longer than one night (<3 months OR: 2.20, 95% CI: 1.39-3.51; 3 months to 1 year OR: 3.00, 95% CI: 1.80-5.01; ≥ 1 year OR: 4.13, 95% CI: 2.40-7.10) were positively associated with knowledge of partner serostatus. Knowledge of partner serostatus was not associated with unprotected anal intercourse with that partner. CONCLUSIONS: Few MSM and TW in Peru know their partners' HIV serostatus. Our findings suggest that the type and length of partnership influence the likelihood of knowing a partner's serostatus. Further research should explore the contexts and practices of partner communication, their effect on sexual behavior, and interventions to promote discussion of HIV testing and serostatus as an HIV prevention strategy in this population.

Human papillomavirus infection in female sex workers in Lima, Peru.

OBJECTIVES: To determine the prevalence and risk factors for human papillomavirus (HPV) infection in female sex workers (FSW) in Lima, Peru. METHODS: Cross-sectional study of 87 FSW. Information regarding demographics, sex work practices, and genital and blood specimens was collected. RESULTS: Forty-four (50.6%) of 87 FSW had HPV detected in cervical swabs. The prevalence of coinfection by two or more HPV types was 39.1%. Thirty-one (35.6%) were infected by at least one high-risk HPV type, representing 70.5% of women with HPV infection. HPV infection was associated with younger age but not with any demographic or sexual characteristics. CONCLUSIONS: Our study confirms the high prevalence of HPV infection in FSW reported by other groups and suggests that brothel-based FSW may be at lower risk for acquiring high-risk HPV infection.

Prevalence of stroke survival in rural communities living in northern Peru.

BACKGROUND AND PURPOSE: Stroke is the leading cause of neurological impairment in the South American Andean region. However, the epidemiology of stroke in the region has been poorly characterized. METHODS: We conducted a staged three-phase population-based study applying a validated eight-question neurological survey in 80 rural villages in Tumbes, northern Peru, then confirmed presence or absence of stroke through a neurologist's examination to estimate the prevalence of stroke. RESULTS: Our survey covered 90% of the population (22,278/24,854 individuals, mean age 30±21.28, 48.45% females), and prevalence of stroke was 7.05/1,000 inhabitants. After direct standardization to WHO's world standard population, adjusted prevalence of stroke was 6.94/1,000 inhabitants. Participants aged ≥85 years had higher stroke prevalence (>50/1000 inhabitants) compared to other stratified ages, and some unusual cases of stroke were found among individuals aged 25-34 years. The lowest age reported for a first stroke event was 16.8 years. High blood pressure (aPR 4.2 [2.7-6.4], p>0.001), and sedentary lifestyle (aPR 1.6 [1.0-2.6], p = 0.045) were more prevalent in people with stroke. CONCLUSIONS: The age-standardized prevalence of stroke in this rural coastal Peruvian population was slightly higher than previously reported in studies from surrounding rural South American settings, but lower than in rural African and Asian regions. The death rate from stroke was much higher than in industrialized and middle-income countries.

Routine laboratory screening for acute and recent HIV infection in Lima, Peru.

BACKGROUND: Before implementing screening programmes for acute HIV infection in developing countries, key issues, including cost, feasibility and public health impact, must be determined. OBJECTIVE: Fourth-generation enzyme immunoassay (EIA) was compared with HIV-1 RNA PCR for the detection of acute and early HIV infection in counselling and testing populations in Lima, Peru. METHODS: Adults presenting for HIV testing at designated clinics in Lima-Callao, Peru were offered additional screening for acute HIV infection. All serum samples were tested with fourth-generation Ag/Ab EIA and confirmed by line immunoassay. Negative specimens were combined into 50-sample pools for HIV-1 RNA screening by PCR analysis in standard pooling algorithms. RNA-positive samples were retested with a third-generation EIA to evaluate the relative sensitivity of standard testing procedures. RESULTS: Between 2007 and 2008 1191 participants were recruited. The prevalence of HIV infection was 3.2% (38/1191; 95% CI 2.2% to 4.2%) overall and 10.5% (25/237; 95% CI 6.6% to 14.5%) among men who reported sex with men (MSM). The prevalence of acute or recent HIV infection was 0.2% (95% CI 0% to 0.4%) overall and 0.8% (95% CI 0% to 2.0%) among MSM. Compared with third-generation EIA testing, both fourth-generation EIA and RNA PCR increased the rate of HIV case identification by 5.3% overall and by 8.0% within the subpopulation of MSM. CONCLUSIONS: Screening for acute HIV infection within Peru's resource-limited public health system was acceptable and detected a high prevalence of acute and recent HIV infection among MSM. Additional efforts are needed to screen for, and prevent, transmission of HIV among MSM in Peru during the acute seroconversion stage.

HIV/STI co-infections, syphilis incidence, and hepatitis B vaccination: the Buenos Aires cohort of men who have sex with men.

In a previous cohort study among 327 men who have sex with men (MSM) in Buenos Aires, an HIV incidence rate of 3.9 per 100 persons-year was reported. Using data from this study, we determined: (a) HIV/STI co-infections; (b) clinical manifestations of incident HIV infections; (c) syphilis incidence and its associated risk factors; and (d) adherence and immune response to hepatitis B virus (HBV) vaccine. During the cohort study, 12 incident HIV infections were found. Within this group, HIV infection alone was most frequent (42%), followed by co-infection of HIV/HBV (33%), and triple co-infection of HIV/HBV/syphilis (25%). The most frequent clinical manifestations among incident HIV cases were: pharyngitis, fever, lymphadenopathy, asthenia, and myalgia. Seven new syphilis infections were detected yielding an incidence rate of 2.4 (95% CI=1.07 - 4.73) per 100 persons-year. Sex work was the only significant risk factor associated with syphilis seroconversion (hazard rate=10.93, p-value=0.033). Only 7% of cohort participants reported having received HBV vaccine. Ninety-percent of the 204 cohort members who agreed to be vaccinated completed the HBV vaccination schedule with an immune response rate of 85%. Our findings suggest the need to increase the access to serologic testing for STI and HBV immunization, as well as the developing of effective HIV/STI behavioral and educational prevention programs among MSM in Buenos Aires.

Epilepsy and neurocysticercosis: an incidence study in a Peruvian rural population.

BACKGROUND: Epilepsy is a serious neurological disorder and neurocysticercosis (NCC), the central nervous system infection by the larvae of Taenia solium, is the main cause of acquired epilepsy in developing countries. NCC is becoming more frequent in industrialized countries due to immigration from endemic areas. Previously reported epilepsy incidences range from 30 to 50/100,000 people in industrialized countries and 90 to 122/100,000 people in developing countries. OBJECTIVES: To determine the incidence of epilepsy in a cysticercosis endemic area of Peru. METHODS: A screening survey for possible seizure cases was repeated biannually in this cohort for a period of 5 years (1999-2004) using a previously validated questionnaire. All positive respondents throughout the study were examined by a trained neurologist in the field to confirm the seizure. If confirmed, they were offered treatment, serological testing, neuroimaging (CT scans and MRI) and clinical follow-up. RESULTS: The cohort study comprised 817 individuals. The overall epilepsy incidence rate was 162.3/100,000 person-years, and for epileptic seizures, 216.6/100,000 person-years. Out of the 8 individuals who had epileptic seizures, 4 had markers for NCC (neuroimaging and/or serology). CONCLUSION: The incidence of epilepsy in this area endemic for cysticercosis is one of the highest reported worldwide.

Human immunodeficiency virus and tuberculosis in Argentina: prevalence, genotypes and risk factors.

The objective of this study was to determine the prevalence and genetic variability of human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted infections (STIs) among 205 patients with clinical diagnosis of tuberculosis (TB) in Buenos Aires in 2001. Infections with hepatitis B virus (HBV), HIV-1, hepatitis C virus (HCV), Treponema pallidum and human T-cell lymphotropic virus types I/II were diagnosed in 37/187 (19.8 %), 35/205 (17.1 %), 22/187 (11.8 %), 13/187 (7.0 %) and 4/181 (2.2 %) patients, respectively. Almost one in three participants (33.1 %) presented at least one infection in addition to TB. Multiresistance to TB drugs (isoniazid plus rifampicin) was detected in the isolates recovered from three patients. Injecting drug use was detected as the main risk factor for HIV, HBV and HCV infections. Of ten patients who died, eight were infected with HIV. HIV genetic characterization showed the presence of two different subtypes. Env subtype F was found in 13/24 samples (54.2 %) and subtype B in 11/24 samples (45.8 %) by heteroduplex mobility assay. Sequencing of the protease/RT region was performed in ten samples: three were characterized as subtype B and seven as B/F recombinants by bootscanning analysis. Phylogenetic analysis of four full-length sequences showed that three were the circulating recombinant form CRF12_BF. The results of this study suggest an urgent need to detect HIV infection in high-risk groups to prevent future HIV transmission as well as morbidity and mortality associated with TB by providing highly active antiretroviral therapy (HAART) and/or TB treatment. Collaboration between TB and HIV programmes seems to be the best approach to decrease the incidence of these diseases, especially in high-prevalence HIV settings.

Prevalence of lifetime abortion and methods of contraception among female sex workers in Bogota, Colombia.

BACKGROUND: The primary objective was to estimate the lifetime prevalence of abortion and the secondary objective was to describe the use of contraceptive methods among female sex workers (FSW) in Bogota, Colombia. STUDY DESIGN: A cross-sectional survey was conducted among FSW. Information on sociodemographic characteristics, contraceptive methods, number of abortions, reasons for abortions and sexual practices was collected. RESULTS: A total of 514 FSW were enrolled. Of these, 264 (53%) had a lifetime abortion. Age, years in sex work and a previous sexually transmitted infection were associated with abortion. A total of 89 FSW(17%) reported no contraception method. Oral contraceptives, use of condoms, female sterilization and intrauterine device insertion were the most common methods of contraception. Women who were poorer, who initiated sex work at a younger age and who reported use of illegal drugs were associated with inconsistent contraception. CONCLUSION: A high lifetime prevalence of abortion and inconsistent contraception was found among FSW in Bogota. There is a need for effective and practical contraceptive methods of family health planning among FSW in Colombia.

Supporting the creation of new institutional review boards in developing countries: the U.S. Naval Medical Research Center Detachment experience.

The U.S. Naval Medical Research Center Detachment (NMRCD) has worked in Peru since 1983, conducting research on diseases of military importance in large part by interacting with multiple research partners across the scientific community of Central America and South America. Over the years, NMRCD has had research collaborations in Guatemala, Nicaragua, Costa Rica, Belize, Honduras, Suriname, Venezuela, Colombia, Ecuador, Bolivia, Chile, Uruguay, Paraguay, and Argentina. In addition to the various infectious diseases research collaborations, NMRCD has supported capacity building for research ethics and the creation of new institutional review boards. This article describes the contributions of NMRCD to research ethics training in Central America and South America, with specific emphasis on the support given to the creation of new institutional review boards.

Evaluation of the GeneXpert MTB/RIF in patients with presumptive tuberculous meningitis.

BACKGROUND: Meningitis caused by Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide. We evaluated the performance of cerebrospinal fluid (CSF) testing with the GeneXpert MTB/RIF assay versus traditional approaches for diagnosing tuberculosis meningitis (TBM). METHODS: Patients were adults (n = 37) presenting with suspected TBM to the Hospital Nacional Dos de Mayo, Lima, Peru, during 12 months until 1st January 2015. Each participant had a single CSF specimen that was divided into aliquots that were concurrently tested for M. tuberculosis using GeneXpert, Ziehl-Neelsen smear and culture on solid and liquid media. Drug susceptibility testing used Mycobacteria Growth Indicator Tube (MGIT 960) and the proportions method. RESULTS: 81% (30/37) of patients received a final clinical diagnosis of TBM, of whom 63% (19/30, 95% confidence intervals, CI: 44-80%) were HIV-positive. 22% (8/37, 95%CI: 9.8-38%), of patients had definite TBM. Because definite TBM was defined by positivity in any laboratory test, all laboratory tests had 100% specificity. Considering the 30 patients who had a clinical diagnosis of TBM: diagnostic sensitivity was 23% (7/30, 95%CI: 9.9-42%) for GeneXpert and was the same for all culture results combined; considerably greater than 7% (2/30, 95%CI: 0.82-22%) for microscopy; whereas all laboratory tests had poor negative predictive values (20-23%). Considering only the 8 patients with definite TBM: diagnostic sensitivity was 88% (7/8, 95%CI: 47-100%) for GeneXpert; 75% (6/8, 95%CI: 35-97%) for MGIT culture or LJ culture; 50% (4/8, 95%CI 16-84) for Ogawa culture and 25% (2/8, 95%CI: 3.2-65%) for microscopy. GeneXpert and microscopy provided same-day results, whereas culture took 20-56 days. GeneXpert provided same-day rifampicin-susceptibility results, whereas culture-based testing took 32-71 days. 38% (3/8, 95%CI: 8.5-76%) of patients with definite TBM with data had evidence of drug-resistant TB, but 73% (22/30) of all clinically diagnosed TBM (definite, probable, and possible TBM) had no drug-susceptibility results available. CONCLUSIONS: Compared with traditional culture-based methods of CSF testing, GeneXpert had similar yield and faster results for both the detection of M. tuberculosis and drug-susceptibility testing. Including use of the GeneXpert has the capacity to improve the diagnosis of TBM cases.

High genetic variability of HIV-1 in female sex workers from Argentina.

BACKGROUND: A cross-sectional study on 625 Female Sex Workers (FSWs) was conducted between 2000 and 2002 in 6 cities in Argentina. This study describes the genetic diversity and the resistance profile of the HIV-infected subjects. RESULTS: Seventeen samples from HIV positive FSWs were genotyped by env HMA, showing the presence of 9 subtype F, 6 subtype B and 2 subtype C. Sequence analysis of the protease/RT region on 16 of these showed that 10 were BF recombinants, three were subtype B, two were subtype C, and one sample presented a dual infection with subtype B and a BF recombinant. Full-length genomes of five of the protease/RT BF recombinants were also sequenced, showing that three of them were CRF12_BF. One FSW had a dual HIV-1 infection with subtype B and a BF recombinant. The B sections of the BF recombinant clustered closely with the pure B sequence isolated from the same patient. Major resistance mutations to antiretroviral drugs were found in 3 of 16 (18.8%) strains. CONCLUSION: The genetic diversity of HIV strains among FSWs in Argentina was extensive; about three-quarters of the samples were infected with diverse BF recombinants, near twenty percent had primary ART resistance and one sample presented a dual infection. Heterosexual transmission of genetically diverse, drug resistant strains among FSWs and their clients represents an important and underestimated threat, in Argentina.

Buenos Aires cohort of men who have sex with men: prevalence, incidence, risk factors, and molecular genotyping of HIV type 1.

The prevalence, incidence, risk factors, and molecular genotyping of HIV-1 infection among men who have sex with men (MSM) were assessed through a prospective cohort study. The study was conducted in Buenos Aires from February 2003 to December 2004. Sociodemographic, sexual risk behavior data, and blood samples for HIV testing were collected at baseline and at 6 and 12 months. Cox regression analysis was applied to determine risk factors associated with HIV seroconversion. HIV-positive samples were analyzed by partial (pro/RT) and full-length genome sequencing. Of 811 HIV-negative participants evaluated at baseline, 327 volunteers that fulfilled the inclusion criteria were enrolled. Retention rates at 6 and 12 months were 97.2% and 91.5%, respectively. Twelve MSM seroconverted for HIV infection [incidence rate = 3.9 (95% CI = 2.0-6.7) per 100 person-years]. HIV seroconversion was associated with a greater number of different sexual contacts in the preceding 6 months (> or =10, hazard ratio = 3.3, 95% CI: 1.1-10.4). By partial pro/RT genotyping analysis, 83% HIV-positive samples were subtype B and 17% samples were BF recombinants, most of these being unique recombinant forms. This study describes for the first time the recruitment and follow-up of a cohort of MSM in Argentina. Retention rates and HIV incidence rate were high. These data should be considered as a promising potential population for HIV vaccine trials.