A. von Gottberg

Impact of conjugate Haemophilus influenzae type b (Hib) vaccine introduction in South Africa

OBJECTIVE To analyse trends in reported invasive Haemophilus influenzae disease in South Africa within the first five years of introduction of conjugate Haemophilus influenzae type b (Hib) vaccine in the routine child immunization schedule. METHODS We used national laboratory-based surveillance data to identify cases of invasive H. influenzae disease between July 1999 and June 2004, and submitted isolates for serotyping and antimicrobial susceptibility testing. FINDINGS The absolute number of Hib cases (reported to the national surveillance system) among children below one year of age decreased by 65%, from 55 cases in 1999-2000 to 19 cases in 2003-04. Enhanced surveillance initiated in 2003, identified human immunodeficiency virus (HIV)-infection and incomplete vaccination as contributing factors for Hib transmission. The total number of laboratory-confirmed cases of H. influenzae remained unchanged because non-type b disease was being increasingly reported to the surveillance system concomitant with system enhancements. Children with non-typable disease were more likely to be HIV-positive (32 of 34, 94%) than children with Hib disease (10 of 14, 71%), P = 0.051. Recent Hib isolates were more likely to be multidrug resistant (2% in 1999-2000 versus 19% in 2003-04, P = 0.001). CONCLUSION Data from a newly established national laboratory-based surveillance system showed a decrease in Hib disease burden among South African children following conjugate vaccine introduction and identified cases of non-typable disease associated with HIV infection.

Impact of cotrimoxazole on non-susceptibility to antibiotics in Streptococcus pneumoniae carriage isolates among HIV-infected mineworkers in South Africa

OBJECTIVES To investigate risk factors for pneumococcal carriage and non-susceptibility among HIV-infected mineworkers in South Africa. METHODS In a cross-sectional study, HIV clinic attendees were questioned about risk factors for pneumococcal carriage and antimicrobial non-susceptibility. Oropharyngeal and nasopharyngeal swabs were taken for pneumococcal culture, serotyping and susceptibility testing. RESULTS Among 856 participants (854 male, median age 41.5years, median CD4 290cells/mm(3)), 294 (34.3%) were receiving cotrimoxazole prophylaxis. Overall, 75/856 (8.8%) carried S. pneumoniae; among those taking vs. not taking cotrimoxazole, 8.2% vs. 9.1% were carriers. Risk factors for pneumococcal carriage were living with a child (adjusted OR 2.12, 95% CI 1.06-4.62) and recent hospitalisation (adjusted OR 1.80; 95% CI 0.98-3.30). Among participants not taking cotrimoxazole, the prevalence of carriage was higher in individuals with lower CD4 counts. Comparing participants taking cotrimoxazole vs. not, 60.9% vs. 22.4% (p=0.001) isolates were non-susceptible to cotrimoxazole and 30.4% vs. 8.2% were non-susceptible to penicillin (p=0.014). Thirty three/72 (45.8%) isolates were paediatric serotypes/groups. Nasopharyngeal compared with oropharyngeal swabs had higher sensitivity in detecting carriage (53/75, 70.7% vs. 31/75, 41.3%), and adding oropharyngeal sampling increased detection from 6.2% to 8.8%. CONCLUSIONS Non-susceptibility to cotrimoxazole and penicillin was more common among isolates from participants taking cotrimoxazole prophylaxis. Surveillance for antimicrobial susceptibility is important where prophylaxis is used. Treatment for pneumococcal disease should take into account a higher risk of non-susceptibility to antibiotics amongst individuals taking cotrimoxazole prophylaxis.

Guidelines for the management of acute meningitis in children and adults in South Africa

This guideline provides a rational and cost-effective approach to patients with acute meningitis, which causes considerable morbidity and mortality, predominantly in children.There are many aetiologies, but a small number of bacteria and viruses account for the majority of cases. There should be a low threshold for suspecting acute meningitis, which is a medical emergency and antibiotics should not be delayed. Blood culture and cerebrospinal fluid (CSF) analysis are the most important diagnostic tests and should be performed whenever it is safe and practical. Contraindications to lumbar puncture are discussed and an algorithm is given regarding administering empiric antibiotics and antivirals, performing blood cultures, computer tomography brain scanning and cerebrospinal fluid analysis, depending on the clinical features and availability of resources. Administration of steroids is not recommended. Guidelines are provided for definitive therapy whenever a causative organism is identified. When no organism is identified, treatment and further investigation should be guided by laboratory results and clinical response. An approach to this process is outlined in a second algorithm. The epidemiology of resistance to common pathogens is described and advice given regarding special groups, including those with recurrent meningitis or base-of-skull fractures. Advice regarding infection control, post-exposure prophylaxis and vaccination is provided.

Part IV. Human infections and antibiotic resistance.

South Africa has a high burden of infectious diseases, including a large portion that are of bacterial origin. This section reviews the national burden of disease and levels of antibiotic resistance in common bacterial infections in the human population. The consequences of resistance on clinical outcomes, through either treatment failures or the development of more virulent infections, are largely unknown. The full impact of antibiotic resistance on health in South Africa therefore remains to be assessed.

Region-specific diversification of the highly virulent serotype 1 Streptococcus pneumoniae.

Serotype 1 Streptococcus pneumoniae is a leading cause of invasive pneumococcal disease (IPD) worldwide, with the highest burden in developing countries. We report the whole-genome sequencing analysis of 448 serotype 1 isolates from 27 countries worldwide (including 11 in Africa). The global serotype 1 population shows a strong phylogeographic structure at the continental level, and within Africa there is further region-specific structure. Our results demonstrate that region-specific diversification within Africa has been driven by limited cross-region transfer events, genetic recombination and antimicrobial selective pressure. Clonal replacement of the dominant serotype 1 clones circulating within regions is uncommon; however, here we report on the accessory gene content that has contributed to a rare clonal replacement event of ST3081 with ST618 as the dominant cause of IPD in the Gambia.

Temporal association of infant immunisation with pneumococcal conjugate vaccine on the ecology of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonisation in a rural South African community.

BACKGROUND Immunisation of children with pneumococcal conjugate vaccines (PCV) may affect the bacterial-ecology of the nasopharynx, including colonisation by Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. The aim of this study was to evaluate the effect of infant PCV-immunisation on the nasopharyngeal ecology of these potentially pathogenic bacteria in a rural African setting. METHODS Two cross sectional surveys were undertaken from May to October in 2009 (Period-1) which coincided with the introduction of 7-valent PCV (PCV7) and in May-October 2011 (Period-2). Consenting household members, where there was a child <2 years of age in residence, had nasopharyngeal swabs undertaken for culture. RESULTS From Period-1 to Period-2 in children 0-2 years and 3-12 years, prevalence of overall S. pneumoniae colonisation decreased from 74.9% to 67.0% (p<0.001) and H. influenzae declined among children 3-12 years (55.1-45.3%, p<0.001) but not among those <2 years. The prevalence of S. aureus remained unchanged in all children. Competitive associations were found between S. pneumoniae and S. aureus and between H. influenzae and S. aureus among children. In individuals >12 years, the prevalence of colonisation decreased from 11.2% to 6.8%, 16.7% to 8.8% and 31.2% to 23.7% for S. pneumoniae, H. influenzae and S. aureus, respectively; p<0.001 for all comparions. Synergistic relationships for S. aureus with H. influenzae and S. pneumoniae were observed in both periods among this group.

An isolated outbreak of diphtheria in South Africa, 2015

An outbreak of respiratory diphtheria occurred in two health districts in the province of KwaZulu-Natal in South Africa in 2015. A multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. Fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. Of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. The case fatality was 27%. Ninety-three household contacts, 981 school or work contacts and 595 healthcare worker contacts were identified and given prophylaxis against Corynebacterium diphtheriae infection. A targeted vaccination campaign for children aged 6-15 years was carried out at schools in the two districts. The outbreak highlighted the need to improve diphtheria vaccination coverage in the province and to investigate the feasibility of offering diphtheria vaccines to healthcare workers.

A century of South African battles against the pneumococcus — ‘the Captain of Death’

A hundred years ago, Sir William Osler described the Pneumococcus as the “Captain of the men of death” referring to John Bunyuan’s phrase in his book, “The life and death of Mr Badman”, written more than 200 years earlier: “Yet the captain of all these men of death that came against him to take him away was the consumption, for it was that that brought him down to the grave”. For Sir William Osler the captain of the men of death was not “consumption” [tuberculosis]) but pneumonia or the pneumococcus. During his time acute pneumonia was responsible for more deaths than tuberculosis and the pneumococcus killed adolescents and young adults in the prime of their lives. Death followed a severe illness with high fever from 105° F to 107° F, fighting for air with rapid and shallow, often painful breathing. The condition escalated to a crisis characterized by a sharp fall in temperature, and in many, death. Concerning those that recover Osler states, “Usually there is an abundant sweat and the patient sinks into a comfortable sleep” and “With the fall in the fever the respirations become reduced almost to normal, the pulse slows, and the patient passes from perhaps a state of extreme hazard and distress to one of safety and comfort”.

The global epidemiology of meningococcal disease: Surveying a shifting terrain

The increasing emergence anduncontrolled spread of antmicrobial resistance worldwide threatens patient outcomes and raises overall healthcare costs. The emergence of antimicrobial resistance combined with the downturn in the development of new antimicrobial agents in the pharmaceutical industry poses unanticipated challenges in the effective management of infection. The question arises, how can we most effectively utilize this invaluable resource, antimicrobials, in the face of ever more difficult to treat infections? This question serves as the fundamental basis for the concept of antimicrobial stewardship (AMS). Antimicrobial stewardship refers to coordinated interventions designed to improve and measure the appropriate use of antimicrobial agents by promoting the selection of the optimal antimicrobial drug regimen including dosing, duration of therapy, and route of administration. The major objectives of antimicrobial stewardship are to achieve best clinical outcomes related to antimicrobial use while minimizing toxicity and other adverse events, thereby limiting the selective pressure on bacterial populations that drives the emergence of antimicrobial-resistant strains. Antimicrobial stewardshipmay also reduce excessive costs attributable to suboptimal antimicrobial use. The implementationof suchaprogram is complicated and requires a wholesystems approach. To be successful, an antibioticstewardship program should be multifaceted and should comprise policies, guidelines, surveillance,prevalence reports, education, and audit practices to optimize prescribing methods There are some factors that are important in crafting effective hospitalbasedantimicrobial stewardshipprograms like ensuring theproper use of antimicrobials to provide the best patient outcomes, lessen the risk of adverse effects, promote cost-effectiveness, and reduce or stabilize levels of resistance. Proper guidelines for the rational use of antibiotics is a cornerstone in any AMS program and should take into account: local epidemiologic data of the hospital where theAMSwill take place, consider themost importantmechanismof resistance of the bacteria involved, incorporate concepts of Selective Pressure in order to choose the right antibiotic for the bacteria thatwill be treated andfinally, once the culture identifies thebacteria, “de-escalation”.