Categories: Sanger Science8 April 20143.7 min read

An underestimated emergency

8th April 2014
By Sam Kariuki

S. Typhimurium's resistance to resistance to Ceftriaxone is one of the scariest scenarios we are dealing with. Credit: David Goulding, Genome Research Limited

S. Typhimurium's resistance to resistance to Ceftriaxone is one of the scariest scenarios we are facing. Credit: David Goulding, Genome Research Limited

Antibiotic resistance becomes critical in situations where the majority of affected people cannot afford alternative and more effective treatments. When you consider that two thirds of the 2.6 million children under the age of five who die each year from infectious diseases caused by bacteria live in developing countries, it becomes clear that something needs to be done.

The burden of these infections, especially acute respiratory infections and diarrhea caused by bacteria, is just beginning to emerge in Africa. The additional effect of immune suppression due to HIV and malnutrition in the 0 to 5 age group compounds the problem further. Unfortunately, less is known about the extent to which antibiotic resistance in sub-Saharan Africa contributes to problems of managing these bacterial infections.

One of the scariest scenarios, which has been unfolding in Kenya for the past three years, regards resistance to Ceftriaxone among S. Typhimurium 313 invasive strains . This is the last line of treatment for life-threatening bacteria in the blood. This bacteremia has a mortality rate of up to 30 per cent in children below five years of age and presently accounts for 5 to 10 per cent of Salmonella isolations.

We are now increasingly isolating this mutidrug-resistant strain type from blood cultures and, worse still, because it’s on a mobile genetic element, the mutidrug-resistant phenotype and ceftriaxone resistance could spread further to other pathogens in the ecosystem.

Other notable and equally scary statistics regard diarrheal and urinary tract infections caused by E. coli, which now has resistance levels at 50 to 75 per cent for commonly available antibacterials. MRSA is increasingly a huge threat to public health and MRSA isolates are frequently multidrug-resistant, with 94 per cent of isolates resistant to trimethoprim-sulphamethoxazole, 92 per cent resistant to erythromycin, 77 per cent resistant to gentamicin, 63 per cent resistant to rifampicin and 65 per cent resistant to clindamycin .

An example of public-health related disease that no longer occurs in developed countries as a result of improved water supply and sanitation is typhoid. Over 75 per cent of all S. Typhi from hospitals in east Africa and Egypt are multiply resistant to commonly available antibacterials, including ampicillin, cotrimoxazole and chloramphenicol. In addition, the proportion of S. Typhi that are both mutidrug-resistant and resistant to acid, with decreased susceptibility to nalidixic to fluoroquinolones (the current drug of choice), has risen from one per cent in 2000 to nearly 35 per cent in 2012.

This grim picture raises a dilemma about where our funds go: do we improve living conditions or treat sick patients?At a local level, we need routine and sustained surveillance to monitor emerging trends and inform policy. Unfortunately, not much investment has been made in laboratory diagnostic services, which are a crucial element in monitoring the effectiveness of currently available antibacterial agents as well detecting emerging new resistance types.

In high-income countries, where the burden of infectious diseases is relatively modest, resistance to first-line antibacterial agents is usually overcome by use of second and third-line agents. However, in developing countries, where the burden of infectious diseases is high, patients with antibacterial resistant infections may be unable to obtain or afford effective second-line treatments. In sub-Saharan Africa the situation is aggravated by poor hygiene, unreliable water supplies, civil conflicts and increasing numbers of immunocompromised people, such as those with HIV, which facilitate both the evolution of resistant pathogens and their rapid spread in the community.

These issues must be tackled to mitigate effects on public health and to reduce the need for antibacterials in the first place. Our team is involved in carrying out sentinel surveillance for antimicrobial resistance among key food borne infections (such as cholera, typhoid, shigella, E. coli) in Kenya and some of our situation analysis reports have formed a good basis for policy change in the Ministry of Health for management of these infections.

Sam Kariuki is currently a chief research scientist at KEMRI and a Sanger International Fellow working on molecular epidemiology of enteric diseases and antimicrobial resistance in Kenya and the region.