HerpeZ

Diagnostics Research & Training in Zambia

Pneumonia

Pneumonia refers to inflammation of the lung, and it can be cause by numerous bacterial, fungal, mycobacterial and viral pathogens [1] Whilst many infections are mild and respond to empirical antibiotic therapy administered through community clinics, severe infections require hospitalization and are life-threatening. WHO data indicate that pneumonia is actually the leading single cause of death globally, in children aged between 1 month and 5 years, accounting for 800,000 paediatric deaths annually [2]. Pneumonia may also be a contributory or leading cause of death in a wider range of paediatric deaths, such as those recorded as due to AIDS, diarrhoea or due to malnutrition.

Sepsis

Sepsis is defined by bacterial infection in the blood causing a systemic inflammatory syndrome. Infection of the blood arises through a wound or a skin abrasion and through internal tissue damage due to infection. It is particularly important in neonates [3], who can become infected vertically during birth, or horizontally through inadequate hygiene and infection control. Sepsis is associated with pneumonia, as when bacterial infections in the lungs (or other organs) are left untreated and are allowed to progress (possibly assisted by weakened immunity in HIV-infected or exposed, and also malnourished children), the resulting tissue damage allows bacilli to leak into the blood stream causing sepsis. Sepsis is particularly important in neonates where it is the most prevalent infectious cause of death, responsible for 421,000 neonatal deaths annually [2].

Meningitis

Once a bacterial infection has entered the blood stream, bacilli are then able to spread and establish foci of infection elsewhere in the body, most notably causing meningitis, defined by inflammation of the meninges and the detection of bacteria in the cerebrospinal fluid. Meningitis is also an extremely important but neglected cause of death, particularly among children and neonates, where it is responsible for 50% more paediatric deaths than AIDS, according to WHO data [2].

High mortality despite availability of antibiotics

How can supposedly treatable bacterial infections be such dominant causes of death, even in settings where antibiotics are readily available? From over 10 years of experience researching infectious disease diagnostics and disease burden at the University Teaching Hospital, Lusaka, Zambia, at HerpeZ we are interested in undertaking research that helps us understand what the causes of this problem are, and ultimately to gather the evidence that will inform on life-saving interventions. 


We postulate that there are three highly probable and non-mutually exclusive factors that likely contribute to the high burden of mortality due to bacterial infections:

  • Late Referral: Even in cities like Lusaka, Zambia, that have a comprehensive network of community clinics and a good referral system, there are large poor communities where, due to lack of education and/or resources, parents might present their children very late to the health system.
  • Co-infection: In high disease burden settings, pneumonia, sepsis and meningitis are primarily diagnosed clinically, and treated empirically with antibiotics. This strategy is simple and affordable, but inadequate, and overlooks possible co-morbidity with viral, mycobacterial and fungal pathogens that also infect the lower respiratory tract.
  • Antibiotic resistance: Widespread misuse of antibiotics has led to high levels of antibiotic resistance [4] and so some deaths may be due to drug resistant bacteria.

All three factors highlight the need for a better understanding of the underlying aetiology of these diseases, and improved diagnostic tools and strategies to better manage these large and neglected patient groups. The relative contribution of non-bacterial causes of pneumonia, sepsis and meningitis needs to be better understood, to guide vaccine, diagnostic and drug development, and to permit more rationale microbiologically informed use of antibiotics.

Most prevalent causes of death in children. Reproduced from Liu et al... Lancet 2015 (PDF)

Research Projects

Useful Links

Check out this amazing real time visualisation of the evolution of antimicrobial resistance from the Kishony lab at Harvard

1. Zar HJ, Madhi SA, Aston SJ, Gordon SB. Pneumonia in low and middle income countries: progress and challenges. Thorax 2013; 68(11): 1052-6.

2. Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, Cousens S, Mathers C, Black RE. Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 2015; 385(9966): 430-40.

3. Seale AC, Obiero CW, Berkley JA. Rational development of guidelines for management of neonatal sepsis in developing countries. Current opinion in infectious diseases 2015; 28(3): 225-30.

4. The Lancet Infectious D. Time for global political action on antimicrobial resistance. The Lancet infectious diseases 2016; 16(10): 1085.

Publications