A review of 40 years of enteric antimicrobial resistance research in Eastern Africa: what can be done better?

The emergence and persistence of antimicrobial resistance is driven by varied factors including the indiscriminate use of antibiotics and variable drug efficacy and presents a major threat to the control of infectious diseases. Despite the high burden of disease in sub-Saharan Africa and the potential health and economic consequences, the level of research on antimicrobial resistance in the region remains unknown. Little data exists to quantify the contribution of different factors to the current levels of antimicrobial resistance. To identify the factors that contribute most to the emergence, amplification, persistence and dissemination of antimicrobial resistance in humans and animals, we used the PRISMA 2009 guidelines to conduct a systematic review of studies on antibiotic-resistant enteric bacteria in Eastern Africa. We searched PubMed and Google Scholar databases and identified 2,155 probable articles, of which 89 studies on humans and 28 on animals remained after full-text review. These were articles from Kenya, Tanzania, Uganda, Ethiopia, Rwanda and Burundi, published between 1974 and 2013, that reported resistance in Salmonella, Shigella, Escherichia coli and Vibrio sp. The majority (98%) of human studies were based on hospital- (rather than community-wide) sampling and although they report high levels of antimicrobial resistance in the region, study design and methodological differences preclude conclusions about the magnitude and trends of antimicrobial resistance. To remedy this, we discuss and propose minimum reporting guidelines for the level of detail that should be explicitly provided for antimicrobial resistance study designs, testing of samples and reporting of results that would permit comparative inferences and enable meta-analyses. Further, we advocate for increased focus on community- rather than hospital-based sampling to provide a better indication of population-wide trends in antimicrobial resistance. This approach, together with the establishment of a robust regional surveillance network, should over time build a pool of evidence-based data useful for policy decisions and interventions aimed at controlling antimicrobial resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13756-014-0041-4) contains supplementary material, which is available to authorized users

Sero – epidemiology of brucellosis in people and their livestock:A linked human – animal cross-sectional study in a pastoralist community in Kenya

BACKGROUND: Brucellosis is associated with massive livestock production losses and human morbidity worldwide. Efforts to control brucellosis among pastoralist communities are limited by scarce data on the prevalence and risk factors for exposure despite the high human-animal interactions in these communities. This study simultaneously assessed the seroprevalence of brucellosis and associated factors of exposure among pastoralists and their livestock in same households. METHODS: We conducted a cross-sectional study in pastoralist communities in Marsabit County – Kenya. A total of 1,074 women and 225 children participated and provided blood samples. Blood was also drawn from 1,876 goats, 322 sheep and 189 camels. Blood samples were collected to be screened for the presence of anti-Brucella IgG antibodies using indirect IgG Enzyme-Linked Immunosorbent Assay (ELISA) kits. Further, Individual, household and herd-level epidemiological information were captured using a structured questionnaire. Group differences were compared using the Pearson's Chi-square test, and p-values < 0.05 considered statistically significant. Generalized mixed-effects multivariable logistic human and animal models using administrative ward as the random effect was used to determine variables correlated to the outcome. RESULTS: Household-level seropositivity was 12.7% (95% CI: 10.7–14.8). The individual human seroprevalence was 10.8% (9.1–12.6) with higher seroprevalence among women than children (12.4 vs. 3.1%, p < 0.001). Herd-level seroprevalence was 26.1% (23.7–28.7) and 19.2% (17.6–20.8) among individual animals. Goats had the highest seroprevalence 23.1% (21.2 – 25.1), followed by sheep 6.8% (4.3–10.2) and camels 1.1% (0.1–3.8). Goats and sheep had a higher risk of exposure OR = 3.8 (95% CI 2.4–6.7, p < 0.001) and 2.8 (1.2–5.6, p < 0.007), respectively relative to camels. Human and animal seroprevalence were significantly associated (OR = 1.8, [95%CI: 1.23–2.58], p = 0.002). Herd seroprevalence varied by household head education (OR = 2.45, [1.67–3.61, p < 0.001]) and herd size (1.01, [1.00–1.01], p < 0.001). CONCLUSIONS: The current study showed evidence that brucellosis is endemic in this pastoralist setting and there is a significant association between animal and human brucellosis seropositivity at household level representing a potential occupational risk. Public health sensitization and sustained human and animal brucellosis screening are required

High prevalence of <i>Rickettsia africae</i> variants in <i>Amblyomma variegatum</i> ticks from domestic mammals in rural western Kenya: implications for human health

Tick-borne spotted fever group (SFG) rickettsioses are emerging human diseases caused by obligate intracellular Gram-negative bacteria of the genus Rickettsia. Despite being important causes of systemic febrile illnesses in travelers returning from sub-Saharan Africa, little is known about the reservoir hosts of these pathogens. We conducted surveys for rickettsiae in domestic animals and ticks in a rural setting in western Kenya. Of the 100 serum specimens tested from each species of domestic ruminant 43% of goats, 23% of sheep, and 1% of cattle had immunoglobulin G (IgG) antibodies to the SFG rickettsiae. None of these sera were positive for IgG against typhus group rickettsiae. We detected Rickettsia africae–genotype DNA in 92.6% of adult Amblyomma variegatum ticks collected from domestic ruminants, but found no evidence of the pathogen in blood specimens from cattle, goats, or sheep. Sequencing of a subset of 21 rickettsia-positive ticks revealed R. africae variants in 95.2% (20/21) of ticks tested. Our findings show a high prevalence of R. africae variants in A. variegatum ticks in western Kenya, which may represent a low disease risk for humans. This may provide a possible explanation for the lack of African tick-bite fever cases among febrile patients in Kenya

Human Infection with Rickettsia felis, Kenya

This flea-borne pathogen was detected in febrile patients in North Eastern Province, Kenya

Evidence of superficial knowledge regarding antibiotics and their use: Results of two cross-sectional surveys in an urban informal settlement in Kenya

<div><p>We assessed knowledge and practices related to antibiotic use in Kibera, an urban informal settlement in Kenya. Surveys was employed at the beginning (entry) and again at the end (exit) of a 5-month longitudinal study of AMR. Two-hundred households were interviewed at entry, of which 149 were also interviewed at exit. The majority (>65%) of respondents in both surveys could name at least one antibiotic, with amoxicillin and cotrimoxazole jointly accounting for 85% and 77% of antibiotics mentioned during entry and exit, respectively. More than 80% of respondents felt antibiotics should not be shared or discontinued following the alleviation of symptoms. Nevertheless, 66% and 74% of respondents considered antibiotics effective for treating colds and flu in the entry and exit surveys, respectively. There was a high (87%, entry; 70% exit) level of reported antibiotic use (past 12 months) mainly for colds/flu, coughs and fever, with >80% of respondents obtaining antibiotics from health facilities and pharmacies. Less than half of respondents remembered getting information on the correct use of antibiotics, although 100% of those who did reported improved attitudes towards antibiotic use. Clinicians and community pharmacists were highly trusted information sources. Paired household responses (n = 149) generally showed improved knowledge and attitudes by the exit survey although practices were largely unchanged. Weak agreement (κ = -0.003 to 0.22) between survey responses suggest both that unintended learning had not occurred, and that participant responses were not based on established knowledge or behaviors. Targeted public education regarding antibiotics is needed to address this gap.</p></div

Endemicity of Coxiella burnetii infection among people and their livestock in pastoral communities in northern Kenya

BackgroundCoxiella burnetti can be transmitted to humans primarily through inhaling contaminated droplets released from infected animals or consumption of contaminated dairy products. Despite its zoonotic nature and the close association pastoralist communities have with their livestock, studies reporting simultaneous assessment of C. burnetti exposure and risk-factors among people and their livestock are scarce.ObjectiveThis study therefore estimated the seroprevalence of Q-fever and associated risk factors of exposure in people and their livestock.Materials and methodsWe conducted a cross-sectional study in pastoralist communities in Marsabit County in northern Kenya. A total of 1,074 women and 225 children were enrolled and provided blood samples for Q-fever testing. Additionally, 1,876 goats, 322 sheep and 189 camels from the same households were sampled. A structured questionnaire was administered to collect individual- and household/herd-level data. Indirect IgG ELISA kits were used to test the samples.ResultsHousehold-level seropositivity was 13.2% [95% CI: 11.2–15.3]; differences in seropositivity levels among women and children were statistically insignificant (p = 0.8531). Lactating women had higher odds of exposure, odds ratio (OR) = 2.4 [1.3–5.3], while the odds of exposure among children increased with age OR = 1.1 [1.0–1.1]. Herd-level seroprevalence was 83.7% [81.7–85.6]. Seropositivity among goats was 74.7% [72.7–76.7], while that among sheep and camels was 56.8% [51.2–62.3] and 38.6% [31.6–45.9], respectively. Goats and sheep had a higher risk of exposure OR = 5.4 [3.7–7.3] and 2.6 [1.8–3.4], respectively relative to camels. There was no statistically significant association between Q-fever seropositivity and nutrition status in women, p = 0.900 and children, p = 1.000. We found no significant association between exposure in people and their livestock at household level (p = 0.724) despite high animal exposure levels, suggesting that Q-fever exposure in humans may be occurring at a scale larger than households.ConclusionThe one health approach used in this study revealed that Q-fever is endemic in this setting. Longitudinal studies of Q-fever burden and risk factors simultaneously assessed in human and animal populations as well as the socioeconomic impacts of the disease and further explore the role of environmental factors in Q-fever epidemiology are required. Such evidence may form the basis for designing Q-fever prevention and control strategies

High Prevalence of Rickettsia africae Variants in Amblyomma variegatum Ticks from Domestic Mammals in Rural Western Kenya: Implications for Human Health

Tick-borne spotted fever group (SFG) rickettsioses are emerging human diseases caused by obligate intracellular Gram-negative bacteria of the genus Rickettsia. Despite being important causes of systemic febrile illnesses in travelers returning from sub-Saharan Africa, little is known about the reservoir hosts of these pathogens. We conducted surveys for rickettsiae in domestic animals and ticks in a rural setting in western Kenya. Of the 100 serum specimens tested from each species of domestic ruminant 43% of goats, 23% of sheep, and 1% of cattle had immunoglobulin G (IgG) antibodies to the SFG rickettsiae. None of these sera were positive for IgG against typhus group rickettsiae. We detected Rickettsia africae–genotype DNA in 92.6% of adult Amblyomma variegatum ticks collected from domestic ruminants, but found no evidence of the pathogen in blood specimens from cattle, goats, or sheep. Sequencing of a subset of 21 rickettsia-positive ticks revealed R. africae variants in 95.2% (20/21) of ticks tested. Our findings show a high prevalence of R. africae variants in A. variegatum ticks in western Kenya, which may represent a low disease risk for humans. This may provide a possible explanation for the lack of African tick-bite fever cases among febrile patients in Kenya

Disentangling the wicked problem of antibiotic resistance

Antimicrobial resistance (AMR) is currently an urgent public health concern worldwide. For low-income regions such as sub-Saharan Africa, absence of surveillance data and systematic investigations of risk factors prevents clear assessment of the impact that AMR has in these communities. There is also no empirically-based guidance for intervention strategies. In chapter one, we use PRISMA guidelines to review 116 journal articles from eastern Africa concerning AMR in people and animals, with the aim of understanding the scale of the problem and contributors to the problem. Over the last 40 years, AMR has reportedly increased, with unregulated antibiotic use invoked to explain the high prevalence of AMR in the region. Nevertheless, we note critical gaps: (i) consistent speculation about the risk factors for AMR without critical examination; (ii) no standardized system of testing and reporting of AMR data; and (iii) lack of community-based studies on AMR in people. Chapter two reports the outcome of two cross-sectional surveys on antibiotic use in an informal settlement (slum) in Kenya. Results from this survey show that residents generally have limited and inconsistent knowledge of antibiotics, including a perceived effectiveness of antibiotics for colds and flu. Chapter three explores how variation in lab resources and deviations from prescribed laboratory protocols might impact estimates of AMR prevalence. For the set of factors investigated, i.e. culture conditions, sample storage, isolate selection and repeated re-isolation, we observe that subtle variations are unlikely to significantly alter prevalence estimates. In chapter four, we use a longitudinal study design to examine how sanitation and antibiotic use impact household- and individual AMR loads in households living within an informal settlement in Kenya. While there is a relationship between reported antibiotic use and resistance to sulfamethoxazole and trimethoprim in children, most of the variance in the distribution of resistant bacteria is explained by sanitation variables. We conclude that although it is possible to design educational interventions based on our findings (chapter 2), such interventions are not likely to have a significant impact on community-level AMR when sanitation challenges continue to impact these communities (chapter 4)

Antibiotic residues and antibiotic-resistant bacteria detected in milk marketed for human consumption in Kibera, Nairobi.

The use of veterinary antibiotics is largely unregulated in low-income countries. Consequently, food producers rarely observe drug withdrawal periods, contributing to drug residues in food products. Drug residues in milk can cause immunogenic reactions in people, and selectively favor antibiotic-resistant bacteria in unpasteurized products. We quantified the prevalence of antibiotic residues in pasteurized and unpasteurized milk, and antibiotic-resistant bacteria from unpasteurized milk sold within Kibera, an informal settlement in Nairobi, Kenya. Ninety-five milk samples (74 pasteurized and 21 unpasteurized) were collected from shops, street vendors or vending machines, and tested for the presence of β-lactam and tetracycline residues using IDEXX SNAP kits. MacConkey agar without- and with antibiotics (ampicillin, 32 μg/ml; tetracycline, 16 μg/ml) was used to enumerate presumptive E. coli based on colony morphology (colony forming units per ml, CFU/ml). β-lactam and tetracycline residues were found in 7.4% and 3.2% of all milk samples, respectively. Residues were more likely to be present in unpasteurized milk samples (5/21, 23.8%) compared to pasteurized samples (5/75, 6.8%); P = 0.039. Two thirds of unpasteurized samples (14/21, 66.7%) contained detectable numbers of presumptive E. coli (mean 3.5 Log10 CFU/ml) and of these, 92.8% (13/14) were positive for ampicillin- (mean 3.2 Log10 CFU/ml) and 50% (7/14) for tetracycline-resistant E. coli (mean 3.1 Log10 CFU/ml). We found no relationship between the presence of antibiotic residues and the presence of antibiotic-resistant E. coli in unpasteurized milk sold within Kibera (P > 0.2)

Proportion of responses for which respondents responded “FALSE” for a set of true-or-false questions regarding the use of antibiotics.

<p>Proportion of responses for which respondents responded “FALSE” for a set of true-or-false questions regarding the use of antibiotics.</p