Do Diagnosis Delays Impact Receipt of Test Results? Evidence from the HIV Early Infant Diagnosis Program in Uganda

Background

There is scant evidence on the association between diagnosis delays and the receipt of test results in HIV Early Infant Diagnosis (EID) programs. We determine the association between diagnosis delays and other health care system and patient factors on result receipt.

Methods

We reviewed 703 infant HIV test records for tests performed between January 2008 and February 2009 at a regional referral hospital and level four health center in Uganda. The main outcome was caregiver receipt of the test result. The primary study variable was turnaround time (time between sample collection and result availability at the health facility). Additional variables included clinic entry point, infant age at sample collection, reported HIV status and receipt of antiretroviral prophylaxis for prevention of mother-to-child transmission. We conducted a pooled analysis in addition to separate analyses for each facility. We estimated the relative risk of result receipt using modified Poisson regression with robust standard errors.

Results

Overall, the median result turnaround time, was 38 days. 59% of caregivers received infant test results. Caregivers were less likely to receive results at turnaround times greater than 49 days compared to 28 days or fewer (ARR = 0.83; 95% CI = 0.70–0.98). Caregivers were more likely to receive results at the PMTCT clinic (ARR = 1.81; 95% CI = 1.40–2.33) and less likely at the pediatric ward (ARR = 0.54; 95% CI = 0.37–0.81) compared to the immunization clinic. At the level four health center, result receipt was half as likely among infants older than 9 months compared to 3 months and younger (ARR= 0.47; 95% CI = 0.25–0.93).

Conclusion

In this study setting, we find evidence that longer turnaround times, clinic entry point and age at sample collection may be associated with receipt of infant HIV test results.     

Botulism—Diagnosis,Management and Public Health Considerations

Botulism is an uncommon but often fatal disease associated with ingestion of a potent neurotoxin present in improperly preserved foods. Exposures to commercially preserved foods with an odd or peculiar taste almost never represent exposure to botulism toxin. Improperly prepared home-canned products which are tasted or consumed without heating are more likely to be associated with botulism.The management of suspect and confirmed cases of botulism is presented by medical epidemiologists in the State Department of Public Health, Bureau of Communicable Disease Control, to provide physicians in California with a practical approach to this problem.     

What Triggers a Diagnosis of HIV Infection in the Tokyo Metropolitan Area? Implications for Preventing the Spread of HIV Infection in Japan

Background

Japan has not succeeded in reducing the annual number of new HIV-infected patients, although the prevalence of HIV infection is low (0.02%).

Methods

A single-center observational study was conducted at the largest HIV clinic in Tokyo, which treats 15% of the total patients in Japan, to determine the reasons for having diagnostic tests in newly infected individuals. HIV-infected patients who visited our clinic for the first time between 2011 and 2014 were analyzed.

Results

The 598 study patients comprised one-third of the total reported number of new patients in Tokyo during the study period. 76% were Japanese MSM. The reasons for being tested which led to the diagnosis was voluntary testing in 32%, existing diseases in 53% (AIDS-defining diseases in 22%, sexually transmitted infections (STI) in 8%, diseases other than AIDS or STIs in 23%) and routine pre-surgery or on admission screening in 15%. 52% and 74% of the study patients and patients presented with AIDS, respectively, had never been tested. The median CD4 count in patients with history of previous testing (315/μL) was significantly higher than that of patients who had never been tested (203/μL, p<0.001).

Conclusions

Only 32% of the newly HIV diagnosed patients were diagnosed because of voluntary testing, and 53% were diagnosed due to presence of other diseases. These results remain unchanged from our previous report 10 years earlier (2000–2004) on newly diagnosed patients at the same clinic. HIV testing has not been widely used by newly diagnosed patients in the Tokyo metropolitan area.     

The “ART” of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban,South Africa

Background

Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa.

Methodology/Principal Findings

We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived ≥10 kilometers from the testing center (RR = 1.37; 95% CI: 1.11–1.71), had a history of tuberculosis treatment (RR = 1.26; 95% CI: 1.00–1.58), or were referred for testing by a health care provider rather than self-referred (RR = 1.61; 95% CI: 1.22–2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors.

Conclusions/Significance

Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.     

ECTOPIC PREGNANCY—Early Diagnosis,Clinical Errors and Conservative Operation

This report of eight years'' experience with extrauterine pregnancy by a single gynecologist is an exposition of how the diagnosis was made or why it was missed.Of 26 diagnoses of ectopic pregnancy, five were false (20 per cent); and in three cases (10 per cent) the diagnosis was not made promptly—a total error of 30 per cent.Ectopic pregnancy will be discovered earlier if obstetric patients are always examined shortly after missing the first menstrual period.A palpable adnexal mass was present in 19 of 21 ectopic pregnancies (90 per cent). A mass was palpable in only one of five cases erroneously diagnosed as ectopic pregnancy (20 per cent).Decidual casts were passed by four patients, two of whom did not have ectopic pregnancy.If two gynecologists do not agree on the question of extrauterine pregnancy, a third opinion should be sought or culdoscopy employed.Enucleation of the conceptus and salvage of the oviduct is advocated.     

PNAS:构建出抵抗HIV的免疫细胞,有望治愈HIV感染

正在一项新的研究中,来自美国斯克里普斯研究所(TSRI)和中国上海科技大学的研究人员开发一种方法将抵抗人类免疫缺陷病毒(HIV)的抗体附着到免疫细胞表面上,从而产生抵抗HIV的细胞群体。在实验室条件下,他们的实验证实这些抵抗性细胞能够快速地替换被HIV感染的免疫细胞,从而有助潜在地治愈HIV感染者。相关研究结果在线发表在PNAS期刊上。在论文通信作者     

NONOBSTRUCTIVE OLIGURIA—Differential Diagnosis

A review is presented of ten years'' experience with the differential diagnosis of oliguria, utilizing the standard tests of renal function with the addition of the phenolsulfonphthalein excretion and urinary chloride measurements. The histories of 60 patients seen in consultation because of 24-hour urinary volume of less than 400 ml were studied in order to clarify the value of these tests. Particular attention was given to the postoperative “dilution state,” the oliguria of which tends to mimic that of “acute tubular necrosis.”In only 25 per cent of the 60 cases was “acute tubular necrosis” responsible for the oliguria. In the remaining 75 per cent of patients, oliguria was due either to the effects of simple dehydration without tubular damage, or to tubular dysfunction on a physiologic rather than an organic basis. Thus, three out of four patients with oliguria required aggressive and specific fluid-electrolyte therapy, often with the intensive use of potassium. One out of four required the opposite in therapy—controlled dehydration without added potassium and, on occasion, peritoneal or extracorporeal dialysis, in order to allow six to ten days for tubular repair.     

The HIV epidemic in China： history, response, and challenge

The first case of AIDS was reported in 1985 in China, but by the early 21st century, the government estimated that there were 840,000 citizens living with HIV/AIDS. The number is increasing rapidly. The major risk groups are injection drug users （IDUSs; 43%） and former plasma donors （27%）, but rates among heterosexual groups are rising rapidly. Sentinel surveillance was initiated in 1986, and now includes IDUs, men-who-have-sex-with-men, sexually transmitted disease clinic attendees, antenatal women, long-distance truck drivers, and sex workers. Although the government was slow to respond to the epidemic in the late 20th century, it has made a vigorous response in the early 21st century. Components of that response include implementation and evaluation of harm reduction programs for IDUs, education to increase knowledge and reduce stigma, treatment and social support for rural and poor HIV/AIDS patients, widespread testing, and increased funding for HIV/AIDS programs. International agencies have been generous in their support of the government initiatives. To successfully combat the epidemic, China needs to develop and train the necessary infrastructure to implement its intervention programs, particularly in the rural areas, to vigorously combat stigma and discrimination, support research especially in the universities and research institutions other than the China Centers for Disease Control, develop a system for efficient exchange of research and program information, and update legislation to reflect the current situation.     

Splenic Subcapsular Hematoma—Ultrasonic Diagnosis

In five patients with varying histories of blunt abdominal trauma, examinations were carried out with ultrasonography and other imaging modalities. In all five patients, large, fluid-filled masses were noted in the left upper quadrant. Two patients had nonpalpable hematomas, but examinations were done because of history and vague clinical symptoms. Three patients had palpable masses. In all five patients there was surgical confirmation of the ultrasonic findings, and all recovered without complications. Ultrasonic tomography offers a convenient noninvasive method for assessing suspected splenic hematoma and can also exclude the possibility in a careful examination.     

MYASTHENIA GRAVIS—Problems in Diagnosis

The possibility of myasthenia gravis must be considered in patients persistently complaining of weakness and fatigue. There may be many difficulties and pitfalls in differentiating myasthenia gravis from other disorders in which muscular weakness is a common complaint.Observation of a group of 36 patients with myasthenia gravis, and another group of 30 cases involving the differential diagnosis of myasthenia gravis, led to a conclusion that a physician should apply criteria carefully before arriving at a diagnosis of myasthenia gravis and instituting drug therapy, since nonmyasthenics may frequently respond with subjective improvement temporarily following administration of cholinergic drugs.Myasthenia gravis may be a more common disorder than was suspected in the past.     

Differential Diagnosis of Malaria on Truelab Uno?, a Portable,Real-Time,MicroPCR Device for Point-Of-Care Applications

Background

Sensitive and specific detection of malarial parasites is crucial in controlling the significant malaria burden in the developing world. Also important is being able to identify life threatening Plasmodium falciparum malaria quickly and accurately to reduce malaria related mortality. Existing methods such as microscopy and rapid diagnostic tests (RDTs) have major shortcomings. Here, we describe a new real-time PCR-based diagnostic test device at point-of-care service for resource-limited settings.

Methods

Truenat^® Malaria, a chip-based microPCR test, was developed by bigtec Labs, Bangalore, India, for differential identification of Plasmodium falciparum and Plasmodium vivax parasites. The Truenat Malaria tests runs on bigtec’s Truelab Uno^® microPCR device, a handheld, battery operated, and easy-to-use real-time microPCR device. The performance of Truenat^® Malaria was evaluated versus the WHO nested PCR protocol. The Truenat^® Malaria was further evaluated in a triple-blinded study design using a sample panel of 281 specimens created from the clinical samples characterized by expert microscopy and a rapid diagnostic test kit by the National Institute of Malaria Research (NIMR). A comparative evaluation was done on the Truelab Uno^® and a commercial real-time PCR system.

Results

The limit of detection of the Truenat Malaria assay was found to be <5 parasites/μl for both P. falciparum and P. vivax. The Truenat^® Malaria test was found to have sensitivity and specificity of 100% each, compared to the WHO nested PCR protocol based on the evaluation of 100 samples. The sensitivity using expert microscopy as the reference standard was determined to be around 99.3% (95% CI: 95.5–99.9) at the species level. Mixed infections were identified more accurately by Truenat Malaria (32 samples identified as mixed) versus expert microscopy and RDTs which detected 4 and 5 mixed samples, respectively.

Conclusion

The Truenat^® Malaria microPCR test is a valuable diagnostic tool and implementation should be considered not only for malaria diagnosis but also for active surveillance and epidemiological intervention.     

Estimated HIV Incidence in California, 2006–2009

Introduction

Accurate estimates of HIV incidence are crucial for prioritizing, targeting, and evaluating HIV prevention efforts. Using the methodology the CDC used to estimate national HIV incidence, we estimated HIV incidence in Los Angeles County (LAC), San Francisco (SF), and California’s remaining counties.

Methods

We estimated new HIV infections in 2006–2009 among adults and adolescents in LAC, SF and the remaining California counties using the Serologic Testing Algorithm for Recent Seroconversion (STARHS). STARHS methodology uses the BED HIV-1 capture enzyme immunoassay to determine recent HIV infections by testing remnant serum from persons newly diagnosed with HIV. A population-based incidence estimate is calculated using HIV testing data from newly diagnosed cases and imputing for persons unaware of their HIV infection.

Results

For years 2007–2009, respectively, we estimated new infections in LAC to be 2426 (95% CI 1871–2982), 1669 (CI 1309–2029) and 1898 (CI 1452–2344) (p<0.01); in SF for 2006–2009, 492 (CI 327–657), 490 (CI 335–646), 458 (CI 342–574) and 367 (CI 261–473) (p = 0.14); and in the remaining California counties in 2008–2009, 2526 (CI 1688–3364) and 2993 (CI 2141–3846) respectively. HIV infection rates among men who have sex with men (MSM) in LAC were 100 times higher than other risk populations; the SF MSM rate was 3 to 18 times higher than other demographic groups. In LAC, incidence rates among African-Americans were twice those of whites and Latinos; persons 40 years or older had lower rates of infection than younger persons.

Discussion

We report the first HIV incidence estimates for California, highlighting geographic disparities in HIV incidence and confirming national findings that MSM and African-Americans are disproportionately impacted by HIV. HIV incidence estimates can and should be used to target prevention efforts towards populations at highest risk of acquiring new HIV infections, focusing on geographic, racial and risk group disparities.     

siRNA, miRNA and HIV： promises and challenges

Small interfering RNA （siRNA） and microRNA （miRNA） are small RNAs of 18-25 nucleotides （nt） in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex （RISC） and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing. The promise of gene silencing has led many researchers to consider siRNA as an anti-viral tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. An example of this may be seen in the case of human immunodeficiency virus type-1 （HIV-1） which is able to evade RNA silencing by either mutating the siRNA-targeted sequence or by encoding for a partial suppressor of RNAi （RNA interference）. On the other hand, because miRNA targeting does not require absolute complementarity of base-pairing, mutational escape by viruses from miRNA-specified silencing may be more difficult to achieve. In this review, we discuss stratagems used by various viruses to avoid the cells＇ antiviral si/mi-RNA defenses and notions of how viruses might control and regulate host cell genes by encoding viral miRNAs （vmiRNAs）.     

HIV and HCV： from Co-infection to Epidemiology, Transmission, Pathogenesis, and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.     

Upper Gastrointestinal Hemorrhage—Diagnosis and Management

The current management of a patient with upper gastrointestinal hemorrhage involves three steps: initial correction of unstable hemodynamics, obtaining the specific diagnosis of the lesion responsible for gastrointestinal blood loss, and therapy directed at the specific bleeding lesion. The current approach to upper gastrointestinal hemorrhage is carrying out upper gastrointestinal endoscopy following stabilization of the patient. Although improved morbidity and mortality statistics have been slow to appear, the use of endoscopy permits appropriate therapy directed at the specific lesion. Specific therapeutic measures have been outlined for seven common causes of upper gastrointestinal hemorrhage. The advent of therapeutic endoscopy promises to bring further advances in therapy in the near future.