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.

Imagine: Multidrug-Resistant GC

SOURCE: Blank S, Daskalakis DC. Neisseria gonorrhoeae – Rising infection rates, dwindling treatment options. N Engl J Med 2018;379:1795-1797.

The United States spends an estimated $182 million annually on the treatment of acute gonococcal infection (GC) (in 2017 dollars). Imagine what would happen to that dollar figure if we lost ceftriaxone as effective therapy for GC.

The Gonococcal Isolate Surveillance Program (GISP) was begun in 1986 to monitor antibiotic resistance in Neisseria gonorrhoeae isolates at selected sites throughout the United States. The first evidence of a serious shift in susceptibility patterns occurred in 2007, with evidence of increasing resistance to fluoroquinolones, along with reports of clinical treatment failure. As a result, fluoroquinolones were removed from recommended treatment guidelines for GC. Subsequently, increasing MICs to cefixime and other oral cephalosporins were observed, and clinical failures to these agents began to appear. Over the past few years, increasing MICs to azithromycin have been observed.

Presently, resistance to ceftriaxone in the United States remains limited to a handful of cases. Fortunately, all isolates with reduced susceptibility to azithromycin have retained sensitivity to ceftriaxone. Although ceftriaxone retains its efficacy for now, the threat of evolving resistance to what is virtually the only remaining reliable therapy looms on our doorstep. Should this occur, it is not at all clear what the best treatment regimen might be — and it may just require days of parenteral treatment.

This editorial underscores the threat by laying out the possible consequences of a further shift in gonorrhea susceptibility patterns: 1) younger, sexually active people will be affected disproportionately, potentially resulting in lost wages and even days of hospitalization; 2) increasing risk of refractory pelvic inflammatory disease in young women, with resulting infertility; 3) increasing risk to pregnant women and neonates, with serious health consequences and adverse pregnancy outcomes (e.g., blindness in neonates); 4) the use of potentially more toxic agents; 5) an increase in HIV infection; and 6) a stunning increase in the annual cost of STD treatment. Safe and reliable agents are needed urgently for the treatment of GC.

A New Borrelia Species in the ‘Old World’

SOURCE: Qiu Y, Nakao R, Hang’ombe BM, et al. Human Borreliosis caused by a New World relapsing fever Borrelia-like organism in the Old World. Clin Infect Dis 2018; Nov 13. doi:10.1093/cid/ciy850. [Epub ahead of print].

While Lyme disease gets all the press, other species of Borrelia can cause significant and sometimes more severe disease. In Africa, relapsing fever is listed in the top 10 causes of mortality in children and is an important cause of perinatal mortality. Research into the evolutionary development of different Borrelia species often identifies which species are “New World” and which ones are “Old World.” However, the story may be complicated by bird and bat species migration, which may play a role in the distribution of these organisms around the world.

As a brief summary, in the New World, epidemic relapsing fever is caused by the louse-borne Borrelia recurrentis, whereas endemic relapsing fever is caused by three different tick-borne Borrelia species (B. hermsii, B. parkeri, and B. turicatae, of which the former is the most common). In the Old World, tick-borne relapsing fever generally is caused by B. duttonii or B. crocidurae, which are recognized causes of relapsing fever, especially in West Africa. However, it has been suspected that other Borrelia species may play a role in relapsing fever in Africa, and other previously unrecognized species have been found in bats.

These authors reported the isolation of a novel Borrelia-like organism from the blood of a 35-year-old man in Zambia, the first time a Borrelia-like organism has been identified as a cause of “relapsing fever” in southern Africa. The young man had entered a cave in Zambia about eight days prior to developing fever, muscle aches, headache, and lassitude. One day later, he presented to the University of Zambia, where a basic workup, including a blood smear for parasites and malaria, was negative. He reported exposure to bats and a “soft tick bite.”

Suspecting a possible zoonotic infection, healthcare providers took blood samples prior to initiation of antibiotics and performed cultures on specialized media (BSK). Molecular testing of blood samples also was performed. The testing isolated a spirochete, and preliminary identification by 16s rDNA and flab analysis suggested a Borrelia-like organism. The patient quickly responded to orally administered erythromycin.

The authors then turned their attention to various bat species found in the cave and their ticks. Fifty ticks were collected from the cave, all of which were identified as Ornithodoros faini, a soft tick. These were subjected to molecular analysis, yielding 20 ticks positive for a Borrelia organism. Subsequent 16S rDNA PCR and sequencing identified an organism remarkably similar to the patient’s isolate (99.6-100% homology). Organ samples of bats previously collected from the cave and stored (for other purposes), as well as blood samples from 38 bats found in the cave, all were tested similarly. Twenty-seven percent yielded a similar organism. Phylogenetic analysis demonstrated the new organism, designated Candidatus B. faini in this study, was remarkably similar to B. recurrentis, despite the fact that the organism was isolated in Africa.

With the use of various molecular methods, many newer species of Borrelia-like organisms are being discovered throughout the world. Some reports suggest that tick ranges and distribution may be affected by climate change — and especially the prolonged droughts in Africa. But it is important to remember that tick-borne infections may occur rarely in travelers returning from Africa.