Literature Review for Antimicrobial Resistance in Sub-Saharan Africa

Introduction

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The review of literature focuses on antimicrobial resistance in Sub-Saharan Africa. The analysis uses available published literature on the topic, specifically in the selected region. The articles included in the review were published between 2010 and 2019 to ensure that all data included is recent. The study concentrates on information relating to the surveillance of antibacterial resistance Sub-Saharan Africa to provide a strong case of the problem and propose effective mechanisms that might reduce the issue and improve the quality of life in the region. Hence, to indicate the significance of the challenge in the area, the review focuses on the magnitude of the problem, the most infectious bacteria resistance, commonly resisted antibiotics, cause of the resistance, and some measures that can be initiated to reduce the level of resistance. Therefore, a total of 16 sources were reviewed to cover these crucial sections.

Antibiotic Resistance

Since they were introduced in the 1940s, antibiotics have played a critical role in modern health care delivery. They have improved and expanded the prevention, treatment, and management of various infections. Antibiotics prevent the spread of infections among surgical patients, protect individuals who have cancer from compromised immunity, and promote growth and prevent diseases in animals and people. Regardless of the achievement made so far, challenges relating to the use of antibiotics are common. The once-treatable infections have become challenging to treat using the available antibiotics. The rate of mortality caused by various infections is increasing in different parts of the world. Individuals and society are facing an increased cost of treatment and disease burden.[1] The world has witnessed a decline in antibiotic effectiveness and a rise in the challenge from a minor drawback in health care to a significant threat to public health.

Most pathogens have become resistant to antibiotics, some to more than one. Problematically, new and last-resort antibiotics are costly and unaffordable to most patients, especially in the third world countries in Sub-Saharan Africa. The problem is a direct outcome of the use of antibiotics in the treatment of various infections. The high volume of their use causes the development of antibiotic-resistant populations. They develop in large numbers to increase their chances of survival. Augmented antibiotic consumption is emanating from two trends. Firstly, the world has experienced an increase in access to antibiotics, appropriately and inappropriately. Hence, the rise in drug use is creating resistance. Secondly, the increasing demand for animal protein has intensified the need for antibiotics in agriculture. Consumption of such foods is another reason for the emergence of the resistance phenomenon. The State of the World’s Antibiotics report has revealed the extent of the challenge in the world.[2] The problem calls for significant research efforts to address the challenge and improve the efficacy of antibiotics.

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The Magnitude of the Problem

Effective interventions can only be developed with knowledge regarding the extent of the problem of antibiotic resistance in Sub-Saharan Africa. Research should focus on the local antimicrobial resistance (AMR) patterns. Modern surveillance approaches provide the necessary information to use in understanding the extent of the issue in a region. Recent reports have indicated alarming rates of (multi)drug-resistant bacteria in the developing world, including Asia and Sub-Saharan Africa. Regardless of the need for such information, countries in Sub-Saharan Africa have remained behind in the collection of data to reveal the actual prevalence of the problem due to the minimal surveillance capacity. Hence, the region continues to experience a high burden of infectious diseases. Recent research indicates an increase in the consumption of antimicrobials in the area. [3] However, a minor repertoire of (poor-quality) antimicrobials is available in most countries, especially over-the-counter, without adequate diagnosis and prescription.

The problem is highly prevalent in Sub-Saharan Africa because of antibiotic consumption practices. The State of the World’s Antibiotics report reveals the trends in various parts of the world, including Sub-Saharan Africa. Although the increase in antibiotics use in the region is not necessarily due to increased income, the region has experienced a growth in the use of affordable antibiotics, which are not necessarily effective. Production of animal proteins is another main reason for the increase in the issue of antibiotic resistance as farmers in the region strive to increase production to meet the ever-rising demand. Evidence reveals a decline in the effectiveness of antibiotics in the region, including all first-line and last-resort antibiotics.[4] The patterns of resistance differ from one country to another, but on the rise nevertheless.

Most Infectious Bacteria Resistant

Research shows various types of bacterial infections that are resistant to commonly used antibiotics. Gonorrhea is one of the leading sexually transmitted infections in Sub-Saharan Africa. Notably, it could be second after human immunodeficiency virus (HIV), particularly in urban centers.[5]  Neisseria gonorrhoeae has emerged as one of the common antibiotic-resistant bacteria in the region. The infectious agent has resisted the commonly used antibacterial agents. Research reveals a recent development of the quinolone-resistant N. gonorrhoeae in sub-Saharan Africa. The bacteria was discovered in 2007 and increased from 9.5% to 50% by 2009.[6] The evidence shows the potential for the antibiotic resistance to cause death or other disabling effects from infectious conditions. As a result, the region has a huge responsibility to eliminate antibiotic resistance infection and reduce its spread.

Besides the quinolone-resistant N. gonorrhoeae, another infectious disease that is causing a high level of resistance to antibiotics is chlamydia. Trachoma-control programs have been responsible for distributing oral azithromycin in the effort to control bacterial infections. Regardless, the ocular strains of chlamydia have remained highly prevalent and increasingly resistant to the antibiotics.[7][8] Previously, Azithromycin has been proven effective in fighting against trachoma despite adverse side effects. However, it has shown to relate to some macrolide-resistant strains of Streptococcus pneumoniae as well as Escherichia coli.[9][10] Sub-Saharan Africa has a high prevalence of some of the most common antibiotic-resistant infections, such as invasive bacterial infections and tuberculosis, among others. The problem is made worse by the fact that these conditions become hard to treat using available and affordable antibiotics.

The Sub-Saharan African countries are at a heightened risk of multidrug-resistant (MDR) organisms because of high dependence on human and animal antibiotics. The region experiences a high rate of Enterobacteriaceae, which leads to the production of extended-spectrum β-lactamases (ESBLs). The infection is one of the common multidrug-resistant (MDR) infections in the region. The infections are common in community-based and hospital-based individuals.[11] These conditions place individuals and hospitals at a higher risk of adverse outcomes, such as death, because of the lack of effective antimicrobials for their treatment and management. Many of these infections are a primary cause of high mortality rates in the region. For example, deaths due to Staphylococcus aureus infections have increased in the region and internationally. Antimicrobial resistance complicates the treatment of these conditions.[12] The area experiences the challenge of receiving effective therapies for the treatment of resistant infections. Furthermore, a growing number of antibiotics that have become resistant is evident in the area.

Common Resisted Antibiotics

Various antibiotics have lost their efficacy in the treatment of bacterial infections because of various reasons. In the treatment of Neisseria gonorrhoeae, resistance has been noted in third-generation extended-spectrum cephalosporins, which are commonly used antibiotics. The resistance is a leading obstacle in the control of sexually transmitted infection. For example, in a cross-sectional study conducted in Northern Uganda, it was found that there was a decline in the susceptibility of gonococcal isolates to tetracycline and erythromycin, ampicillin, and ciprofloxacin.[13] The researchers also revealed immediate resistance to chloramphenicol. In another study involving a sample of men in western Kenya, penicillin was found to have 65% resistance, while plasmid-mediated tetracycline was found to have 97% resistance rate.[14] Many of these resisted antibiotics are still available in the market and are ineffective in treating the common infections in the region.

Cheap and unregulated antibiotics are available in the market in Sub-Saharan Africa. They continue to be used in managing infections that require antibiotics as part of their treatment and management. Unregulated antibiotics are sold in drug stores and shops for human and animal use.[15] Many of the low-quality antibiotics are imported at a lower price compared to high-quality drugs from China and India, among other countries. The existence of counterfeit antibiotics has worsened the resistance problem in Sub-Saharan Africa. The health care systems and pharmaceutical industries have to contend with the growth in the number of counterfeit drugs in the market. Antibiotics are approximated at 5% of the international antibiotic industry.[16] Unfortunately, most of the drugs are sold in the developing world, including in Sub-Saharan Africa. The developing countries create a lucrative market for cheap counterfeit medications due to the high demand.

The leading market for counterfeit antibiotics includes emerging economies. Most of the drugs that come from South-East Asia, India and China, find their way to the developing nations due to the high demand. Sub-Saharan Africa is the destination of about 30% of these drugs. Others are sold in South-East Asia, North America, and other regions in the world. Counterfeit antibiotics are those that have been generally utilized for years, such as “beta-lactams: 50%; quinolones: 12%; macrolides, lincosamides, and synergistins: 1%; cyclins: 7%; others: 20%”.[17] Such drugs have various adverse effects on the patient’s body. If consumed regularly, they affect the patient’s health. Besides, they are the leading cause of the development of bacterial resistance with a global effect. They are one of the leading risk factors for antibiotic resistance in developing countries.

The Cause of Resistant

Research reveals various factors that cause antibiotic resistance among patients in Sub-Saharan Africa. Complex socioeconomic and behavioral causes are implicated in the development of antibiotic resistance.[18] One of the most important factors is the economic incentive to use some categories of antibiotics instead of others. Significant profits go to the health care facility after the sales of drugs. Expensive, second-line antibiotics are mostly subscribed to insured patients as opposed to those who lack health coverage. Besides, patients demand prescriptions, depending on their capacity to pay. Economic factors for the prescription, dispensing, and purchase of specific types of drugs play an essential role in creating the problem of resistance. Although adequate information is lacking regarding the supply and demand of antibiotics, it is evident that the prices and availability of resources determine the generation of antibiotic the patient is likely to take. For example, in an impoverished informal settlement in Kenya, about three-quarters of pharmacists reveal that patients cannot afford to have the right prescription of antibiotics and other drugs because of the resource limitation.[19] They cannot afford the complete regimens, or they experience challenges with finances for drugs that their doctors recommend.

Apart from the economic incentive as a factor behind the high rate of antibiotic resistance in Sub-Saharan Africa, inadequate hygiene and infection control could also play a critical role. Most hospitals lack proper hygiene in their environment and among health care providers, placing patients and others at the risk of (multi) drug-resistant pathogens.[20] Such infections spread quite fast between individuals who come into contact with them. Lack of proper infection control also affects the effectiveness of some of the commonly used antibiotics in the region. Failure to have operational mechanisms for the prevention of nosocomial or healthcare-associated infections have led to the high demand for antibiotics and the resultant resistant. Health care facilities in the region also lack adequate knowledgeable health care providers to fight infections effectively. As a result, many countries are affected by the problem of antibiotic-resistant and associated effects.

Besides the issue of hygiene and infection control, antibiotics are used in hospitals without proper diagnostic procedures, which should recommend suitable treatment. In hospitals and clinics in Sub-Saharan Africa, there is an acute lack of appropriate diagnostic resources and subsequent therapy. The challenge places patients at the risk of clinical syndromes, which are susceptible to severe bacterial infections and might require increased use of antibiotics to treat. Many patients use antibiotics because of conditions that might not necessitate the treatment regime due to the wrong diagnosis. The high dependence on such drugs creates the risk of a high level of resistant.[21] The problem might also emerge when treatment usually meant for second-line, third-line, or fourth-line infection management in developed economies is used in Sub-Saharan Africa.[22] These therapies are used in an environment that lacks expert advice, supportive microbiological facilities, or sufficient prescription controls. Such issues can lead to a high level of resistance to the treatments.

The Consequences of Resistance

Few studies in Sub-Saharan Africa have assessed the social and economic costs of antibiotic resistance, especially among the common infectious conditions. A study conducted in Tanzania investigated the prevalence of bloodstream infection as well as risk factors for a fatal consequence of antibiotic resistance. The prospective cohort study used a sample of 1828 among individuals aged between 0 and 7 years admitted with presentations of systemic bacterial infection. The study revealed that antibiotic resistance is a critical risk factor for adverse patient outcomes, including death.[23] Studies in resource-rich nations have shown similar negative consequences of antibiotic-resistant bacteria-caused infections. The infections are a leading cause of high mortality rates in Sub-Sharan Africa and globally. Besides the high mortality rates, the infections lead to more extended hospital stays and a high cost of care.[24] Generally, they have poor outcomes compared to individuals with antibiotic-susceptible infections.

Research has documented the detrimental effects of antibiotic resistance in the developing world. A systematic review of the literature documented the actual effects. Resistance to antibiotic drugs has been implicated with increased morbidity and mortality in the region. They are also responsible for a prolonged time of infectiousness that places other people at the risk of infectious organisms. Such infections, especially in healthcare facilities, are responsible for various hospital-acquired infections. They are the primary reason for the increasing burden of infectious diseases in developing countries.[25] Resistance causes the need for more expensive treatment, which might be unaffordable in the developing countries in Sub-Saharan Africa.

Recommended Solutions

The beginning step in addressing the problem of antibiotic resistance in Sub-Saharan Africa is to implement effective surveillance to understand the extent of the problem. The challenge in the region is the lack of effective surveillance mechanisms to provide reliable data to support intervention initiatives. Since continent-wide surveillance of drug resistance in the region is lacking, the World Health Organization recommends relevant surveillance tools in individual countries. The information can be aggregated to establish the magnitude of the problem in the entire region. Besides, it is critical to continue conducting the analyses and reviews to determine the prevalence of antibiotic resistance in the area. The discussions can focus on specific age groups, a particular sub-regions, clinical syndrome, or class of antibiotics as long as they provide necessary information to use in implementing interventions to overcome the problem.

Besides effective surveillance and assessment of the problem to implement effective interventions, medical experts should explore some of the effective antibiotic treatments that can be used to overcome the resistance issue. For example, researchers have revealed the potential efficacy of azithromycin in preventing some infectious conditions, such as infectious diarrhea, malaria, and pneumonia. According to case-control study findings as well as results of a cluster-randomized trial conducted in a particular region of Ethiopia, proper use of azithromycin to treat trachoma has been revealed to reduce the high rate of childhood mortality.[26] Therefore, medical professionals should conduct further reviews to establish antibiotics that can still be useful in the treatment of infections. Besides, they should educate health care providers, pharmacists, and patients about the need for proper use of antibiotics to prevent resistance. After all, many infectious conditions still require effective antibiotic treatment and responsible use to achieve positive results.

Conclusion

The literature review focuses on the problem of antibiotic resistance in Sub-Saharan Africa. The search led to 16 articles that covered various aspects of the topic, such as the definition of antibiotic resistance, the extent of the problem in the region, the commonly resisted antibiotics and the resistant organisms, and the causes and consequences of the problem. Antibiotic resistance in the area is a pressing threat to public health and the effective operation of healthcare systems. It is a risk to the significant achievements made in the development of antibiotics in the 20rth century. As a result, it is essential to establish strategies to resolve the issue and create effective treatments by focusing on the cause. Therefore, more research is necessary to establish the actual reason for drug resistance in order to implement timely and effective interventions. Researchers and medical experts are responsible for executing effective solutions to the challenge and improving health and wellbeing in the region.

[1] Hellen Gelband, Petrie Molly Miller, Suraj Pant, Sumanth Gandra, Jordan Levinson, Devra Barter, Andrea White, and Ramanan Laxminarayan. “The state of the world’s antibiotics 2015.” Wound Healing Southern Africa 8, no. 2 (2015): 31

 

[2] Hellen Gelband et al. 30.

[3] Stije J. Leopold, Frank van Leth, Hayalnesh Tarekegn, and Constance Schultsz. “Antimicrobial drug resistance among clinically relevant bacterial isolates in sub-Saharan Africa: a systematic review.” Journal of Antimicrobial Chemotherapy 69, no. 9 (2014): 2337.

[4] Hellen Gelband, Petrie Molly Miller, Suraj Pant, Sumanth Gandra, Jordan Levinson, Devra Barter, Andrea White, and Ramanan Laxminarayan, 31.

[5] Samuel Kariuki, and Gordon Dougan. “Antibacterial resistance in sub-Saharan Africa: an underestimated emergency.” Annals of the New York Academy of Sciences 1323, no. 1 (2014): 43.

[6] Antibacterial resistance in sub-Saharan Africa. 43

[7] Hugh R. Taylor, Matthew J. Burton, Danny Haddad, Sheila West, and Heathcote Wright. “Trachoma.” The Lancet 384, no. 9960 (2014): 2142.

[8] Emerson, Paul M., Pamela J. Hooper, and Virginia Sarah. “Progress and projections in the program to eliminate trachoma.” PLoS Neglected Tropical Diseases 11, no. 4 (2017): e0005402.

 

[9] Alison H. Skalet, Vicky Cevallos, Berhan Ayele, Teshome Gebre, Zhaoxia Zhou, James H. Jorgensen, Mulat Zerihun et al. “Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial.” PLoS medicine 7, no. 12 (2010): e1000377.

[10] Anna C. Seale, Mark R. Davies, Kirimi Anampiu, Susan C. Morpeth, Sammy Nyongesa, Salim Mwarumba, Pierre R. Smeesters et al. “Invasive group A Streptococcus infection among children, rural Kenya.” Emerging Infectious Diseases 22, no. 2 (2016): 224.

[11] Phoebe CM. Williams, David Isaacs, and James A. Berkley. “Antimicrobial resistance among children in sub-Saharan Africa.” The Lancet Infectious Diseases 18, no. 2 (2018): e33-e44.

[12] Dennis Nurjadi, Adesola O. Olalekan, Franziska Layer, Adebayo O. Shittu, Abraham Alabi, Beniam Ghebremedhin, Frieder Schaumburg et al. “Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing human infection and colonization in sub-Saharan Africa and its import to Europe.” Journal of Antimicrobial Chemotherapy 69, no. 9 (2014): 2361-2368..

 

[13] Samuel Kariuki, and Gordon Dougan. “Antibacterial resistance in sub-Saharan Africa: an underestimated emergency.” Annals of the New York Academy of Sciences 1323, no. 1 (2014): 43.

 

[14] Antibacterial resistance in sub-Saharan Africa, 43.

 

[15] Phoebe CM. Williams, David Isaacs, and James A. Berkley. “Antimicrobial resistance among children in sub-Saharan Africa.” e35.

[16] A Delepierre, A. Gayot, and A. Carpentier. “Update on counterfeit antibiotics worldwide; public health risks.” Medecine et maladies infectieuses 42, no. 6 (2012): 247.

[17] A Delepierre, A. Gayot, and A. Carpentier, 247.

[18] James A. Ayukekbong, Michel Ntemgwa, and Andrew N. Atabe. “The threat of antimicrobial resistance in developing countries: causes and control strategies.” Antimicrobial Resistance & Infection Control 6, no. 1 (2017): 47.

 

[19] Jackson K. Mukonzo, Proscovia M. Namuwenge, Gildo Okure, Benjamin Mwesige, Olivia K. Namusisi, and David Mukanga. “Over-the-counter suboptimal dispensing of antibiotics in Uganda.” Journal of Multidisciplinary Healthcare 6 (2013): 303.

 

[20] Leopold, Stije J., Frank van Leth, Hayalnesh Tarekegn, and Constance Schultsz. “Antimicrobial drug resistance among clinically relevant bacterial isolates in sub-Saharan Africa: a systematic review.” Journal of Antimicrobial Chemotherapy 69, no. 9 (2014): 2337-2353.

 

[21] Phoebe CM, Williams, David Isaacs, and James A. Berkley. “Antimicrobial resistance among children in sub-Saharan Africa.”e34.

[22]  Reddy, Elizabeth A., Andrea V. Shaw, and John A. Crump. “Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis.” The Lancet Infectious Diseases 10, no. 6 (2010): 417.

 

[23] Samuel Kariuki and Gordon Dougan, 43.

 

[24] Patrick D. Mauldin, Cassandra D. Salgado, Ida Solhøj Hansen, Darshana T. Durup, and John A. Bosso. “Attributable hospital cost and length of stay associated with health care-associated infections caused by antibiotic-resistant gram-negative bacteria.” Antimicrobial Agents and Chemotherapy 54, no. 1 (2010): 109.

[25] Ramanan Laxminarayan and David L. Heymann. “Challenges of drug resistance in the developing world.” Bmj 344 (2012): e1567.

 

[26] Keenan, Jeremy D., Robin L. Bailey, Sheila K. West, Ahmed M. Arzika, John Hart, Jerusha Weaver, Khumbo Kalua et al. “Azithromycin to reduce childhood mortality in sub-Saharan Africa.” New England Journal of Medicine 378, no. 17 (2018): 1583-1592.

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