By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

Tuberculosis Transmission From NAAT-negative Patients

SOURCE: Xie YL, Cronin WA, Proschan M, et al. Transmission of Mycobacterium tuberculosis from patients who are nucleic acid amplification test-negative. Clin Infect Dis 2018; doi: 10.1093/cid/ciy365. [Epub ahead of print].

One of the earlier uses of strain genotyping in a cohort of tuberculosis (TB) patients in San Francisco in the 1990s led to the recognition that AFB smear-negative/culture-positive patients resulted in at least 17% of TB transmission. More recently, rapid nucleic acid amplification (NAA)-based tests are used to evaluate patients with possible TB. NAA testing (either the Xpert MTB/RIF Version G4 or the Amplified Mycobacterium Tuberculosis Direct test [MTD]) is believed to be highly sensitive for the detection of TB in respiratory specimens, with a sensitivity somewhere between sputum smear and culture. The negative predictive value of NAAT on one or two respiratory specimens is comparable to three negative smears and is used increasingly to remove patients more quickly from respiratory precautions or voluntary isolation. The TB transmission risk from NAAT-negative patients who ultimately have positive respiratory cultures has not been studied.

The authors retrospectively examined the risk of TB transmission in a cohort of 809 culture-positive cases in whom NAA testing was performed routinely between 2004-2009. Patients had at least one respiratory culture that was positive for MTB and also had smears performed on three or more respiratory specimens and NAA testing from one or more respiratory specimens. The primary outcome of the study was the transmission risk of a test-negative case, with smear and NAA testing examined separately. A secondary outcome was the minimum transmission risk combining smear and NAAT status.

Genotyping was available on 782 (97%) patients. Of these, 393 had no genotype matches, and the remaining 389 patients “clustered” into 158 groups. This left 83 clusters with 231 secondary cases within the study window. Forty-nine clusters had a recognized index case, which consisted of 47 NAAT-positive index cases, two NAAT-negative index cases, and 113 secondary cases. Based on this, the minimal TB transmission risk from a NAAT-negative case was 5.1% (95% confidence interval [CI], 0-11.4%); and the estimated TB transmission risk from a NAAT-positive case was 35.4% (95% CI, 26-43.2%).

The two NAAT-negative cases (one was known to be HIV negative, the other’s HIV status was not known) were both smear negative, and the patients began TB treatment about one month after collection of their first culture-positive sputum. Importantly, of those 10 cases that were NAAT-negative on two or more respiratory specimens, the risk of TB transmission was zero.

Similarly, the minimum transmission risk from a smear-negative index case was 11.2%, and the estimated risk from a smear-positive case was 47.7%. Eighteen transmission events from 17 smear-negative cases accounted for 9.2% of TB transmission. Combining smear-negative/NAAT-negative cases, the minimum risk of TB transmission was 1.8% — still not zero.

There are several reasons why patients with negative smears and/or NAA may transmit organism: the quality of the specimens tested, the time of day the specimen was obtained, and delays in treatment, during which a patient could develop worsening disease. Initiation of treatment often is delayed in such patients compared to those who are smear- or NAA-positive. These data reinforce the need for prompt initiation of treatment when clinical suspicion is high, even when smears and/or NAA testing are negative.

Recently, I saw such a case — a young man with a small RUL reticulonodular infiltrate, who was both smear (x3) and NAAT-negative. By the time I saw him in consultation in the office, he was clinically improved with a Z-pak, although the chest radiograph was unchanged. Four weeks later, sputum cultures were positive for TB. I believed the tests and not the case.

Worldwide Rabies Risk: Dogs

SOURCE: ProMED-mail post. Rabies (51): Asia (Viet Nam) Africa (Morocco) human, canine. Oct. 3, 2018. Available at: Accessed Oct. 9, 2018.

Rabies remains a significant problem worldwide, especially in India, Southeast Asia, and Africa. The World Health Organization estimates that rabies results in ~59,000 deaths annually in 150 countries, although most of these deaths are concentrated in Asia and Africa. About half occur in children younger than 15 years of age. At least 20,000 deaths occur annually in India alone, generally from stray dog bites. In fact, it is estimated that 99% of global rabies deaths are dog-related.

Most of the time, in the comfort of the United States, we don’t realize the global risk of rabies, until we are traveling and bitten by an animal. I’ve been involved with patients, friends, and family bitten by stray dogs in Belize, Thailand, India, and Turkey and by wild monkeys in Southeast Asia and Indonesia. One patient even was spit on by a camel in Egypt, and another was bitten by an angry pack mule on a trek. More than 15 million people receive post-dog-bite rabies vaccination every year, at an estimated cost of $1.5 billion.

Globally, there is a goal to eliminate human rabies from dog exposure by 2030. Efforts have focused on improved access to post-exposure prophylaxis as well as rabies vaccination of dogs. Rabies vaccine programs are being implemented in many countries, but in some countries the problem persists.

This ProMED mail alert highlights the problem in Morocco, where 65,000 people received post-exposure prophylaxis in 2017. Ninety percent of these individuals were bitten or scratched by a rabid dog. Four hundred cases of animal rabies are reported in Morocco every year. Although Morocco is doing a good job of providing post-exposure prophylaxis to those exposed, the country lacks an organized dog vaccine program, in part because of a lack of information on the number of strays.

The Association of Southeast Asian Nations (ASEAN) has implement a regional strategy to eliminate human rabies by 2020, and many individual countries in this region have begun implementing programs to stamp out rabies. Recognizing a significant problem, Vietnam, for example, has implemented a well-funded nationwide program to eliminate all rabies by 2021.

But there is one area that remains a point of vulnerability, and that is the dog meat trade. Transporting, slaughtering, and butchering dogs and even ingesting infected meat remains an identifiable risk for rabies infection. Several reports document the risk of rabies from dog meat. The dog meat market in Asia remains quite active. For example, Vietnam estimates that 20,000 dogs are transported from south to north Vietnam every month for slaughter and use as food.

Unfortunately, some of the dogs captured and smuggled for slaughter in fact may be sick, sometimes with rabies. The authors of this article report that more than 80 animal rights organizations and charities have signed an open letter to global governments to take action to end the dog meat market, in part to end rabies virus transmission throughout Asia.

Patients Need to Rethink the ‘Quality’ in Healthcare

SOURCE: Fenton JJ, Jerant AF, Bertakis KD, Franks P. The cost of satisfaction: A national study of patient satisfaction, health care utilization, expenditures, and mortality. Arch Intern Med 2012;172:405-411.

Patient satisfaction increasingly is an important and commonly used surrogate marker for healthcare quality. In addition, reimbursement to physicians may be based on patient satisfaction as a “quality” metric. But the evidence linking a patient’s subjective sense of satisfaction and the actual delivery of quality care remains tenuous, at best. These authors conducted a prospective cohort study of 51,946 adults participating in the national Medical Expenditure Panel Survey from 2000-2007. The researchers compared patient satisfaction (based on five items from the Consumer Assessment of Health Plans Survey) at one year with healthcare expenditures (total cost, prescription drug cost) and healthcare utilization (ED visits, hospitalization) at two years, and mortality. Mortality figures were assessed at an average of 3.9 years of follow-up.

The data were adjusted for demographics, health status, chronic illness, insurance status, and socioeconomic status. In brief, the authors found that those with the highest level of satisfaction had the highest level of healthcare costs and the highest rates of mortality. Patients in the highest quartile for year 1 patient satisfaction had an adjusted 8.8% greater healthcare expenditure at year 2, and 9.1% higher prescription drug costs at year 2. They also exhibited a 12% greater risk of hospitalization (adjusted odds ratio, 1.12; P = 0.02) and a 26% greater risk of mortality (adjusted hazard ratio, 1.267; P = 0.02).

The risk of mortality remained significantly higher even when researchers eliminated patients with three or more diseases or the worst self-rated health scores from the analysis. Only the risk of going to the ED appeared lower in those more satisfied.

How to make sense of this? My basic Midwestern way of thinking would like to suggest that the wrong questions are being asked. Perhaps we’ve trained patients to think about their healthcare in the wrong way. How many times have I heard patients complain that their surgeon wasn’t warm? I’ve had to explain, you don’t want your surgeon to be warm and fuzzy, you want him or her to do an excellent job at surgery.

Our large, multi-specialty clinic randomly contacts 10 of our patients per month with a lengthy questionnaire, detailing their satisfaction with their visit. This includes a few questions about their actual visit with the doctor (e.g., Did the doctor listen to your concerns?), but also questions such as “Were the chairs in the waiting room comfortable?” and “Was the parking adequate?” As best I can tell, all it takes is one in 10 patients who hated their experience, for whatever reason, to skew the results. Aside from the cost of generating all these data, how relevant is it? I don’t know, but when I go to the movies and think about the movie, I don’t think about the parking lot or fault the acting because the popcorn didn’t have enough butter.

The most demanding patients may not be the most satisfied, unless of course they get everything they want, which simply cannot translate into the best healthcare. I have a patient who loves her plastic surgeon. He’s good looking and so friendly, he gave her a discount for her last surgery, and she raves that the facility is so gorgeous, there are wait staff who take her drink orders; it’s like going to the spa. Never mind the nasty infection she had for a routine tummy tuck. She still loves the guy.

My male partner has read that patients trust their male doctors more when their shoes are polished, they wear a nice watch, and their shirt is ironed, so he makes sure to polish his shoes every day he’s on call, wears a conspicuous gold watch, and gets his shirts pressed. Patients believe male doctors should look like successful salesmen because they don’t know what else to think.

Although access to parking is important, I am concerned we are training patients to rate their subjective “experience” as a measure of healthcare quality, rather than educating them on how to assess the actual appropriateness and quality of their care. We need to train patients to understand what is important for their healthcare. If you want quality, look at physicians’ evaluations of each other, their referral base, and other hard indicators, like surgical outcomes and infection rates, not the color of the chairs in the waiting room.