Cost-effectiveness analysis of typhoid conjugate vaccines in an outbreak setting: a modeling study

BackgroundSeveral prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant Salmonella Typhi. The World Health Organization recommends the use of typhoid conjugate vaccines (TCVs) in outbreak settings; however, current data are limited on how and when TCVs might be introduced in response to outbreaks.MethodologyWe developed a stochastic model of typhoid transmission fitted to data from Queen Elizabeth Central Hospital in Blantyre, Malawi from January 1996 to February 2015. We used the model to evaluate the cost-effectiveness of vaccination strategies over a 10-year time horizon in three scenarios: (1) when an outbreak is likely to occur; (2) when an outbreak is unlikely to occur within the next ten years; and (3) when an outbreak has already occurred and is unlikely to occur again. We considered three vaccination strategies compared to the status quo of no vaccination: (a) preventative routine vaccination at 9 months of age; (b) preventative routine vaccination plus a catch-up campaign to 15 years of age; and (c) reactive vaccination with a catch-up campaign to age 15 (for Scenario 1). We also explored variations in outbreak definitions, delays in implementation of reactive vaccination, and the timing of preventive vaccination relative to the outbreak.ResultsAssuming an outbreak occurs within 10 years, we estimated that the various vaccination strategies would prevent a median of 15-60% of disability-adjusted life-years (DALYs). Reactive vaccination was the preferred strategy for WTP values of $0-300 per DALY averted. For WTP values >$300, introduction of preventative routine TCV immunization with a catch-up campaign was the preferred strategy. Routine vaccination with a catch-up campaign was cost-effective for WTP values above $890 per DALY averted if no outbreak occurs and >$140 per DALY averted if implemented after the outbreak has already occurred.ConclusionsCountries for which the spread of antimicrobial resistance is likely to lead to outbreaks of typhoid fever should consider TCV introduction. Reactive vaccination can be a cost-effective strategy, but only if delays in vaccine deployment are minimal; otherwise, introduction of preventive routine immunization with a catch-up campaign is the preferred strategy

Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.

An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.This work was supported by the Wellcome Trust. We would like to thank the members of the Pathogen Informatics Team and the core sequencing teams at the Wellcome Trust Sanger Institute (Cambridge, UK). We are grateful to D. Harris for work in managing the sequence data

Epidemiology of hepatitis B, C and D in Malawi:systematic review

BACKGROUND:Viral hepatitis is an important public health issue in sub-Saharan Africa. Due to rising mortality from cirrhosis and hepatocellular carcinoma and limited implementation of screening and treatment programmes, it has been characterised as a neglected tropical disease. Synthesis of the existing evidence on the epidemiology of viral hepatitis B, C and D in Malawi is required to inform policy and identify research gaps. METHODS:We searched Pubmed, EMBASE and Scopus for studies reporting the epidemiology of viral hepatitis B, C and D in Malawi from 1990 to 2018. Articles reporting prevalence estimates were included provided they described details of participant selection, inclusion criteria and laboratory methods (detection of HBsAg, anti-HCV or anti-HDV antibody, HCV antigen or HCV RNA or HDV RNA). We assessed study quality using a prevalence assessment tool. Where appropriate, a pooled prevalence was calculated using a DerSimonian Laird random effects model. RESULTS:Searches identified 199 studies, 95 full text articles were reviewed and 19 articles were included. Hepatitis B surface antigen (HBsAg) seroprevalence was assessed in 14 general population cohorts. The pooled prevalence among adults was 8.1% (95% CI 6.1, 10.3). In 3 studies where HBsAg was stratified by HIV status, no effect of HIV on HBsAg prevalence was observed (OR 1.2 (95% CI: 0.8, 1.6, p = 0.80)). In a single study of HIV/HBV infected individuals, anti-hepatitis D antibody (anti-HDV) prevalence was low (1.5%). HCV antibody prevalence (anti-HCV) ranged from 0.7 to 18.0% among 12 cohorts in general populations. Among three studies which used PCR to confirm current infection, the pooled rate of HCV RNA confirmation among anti-HCV positive individuals was only 7.3% (95% CI: 0.0, 24.3). CONCLUSIONS:Hepatitis B is highly prevalent in Malawi. There is a paucity of epidemiological data from rural areas where 85% of the population reside, and the Northern region. Priority research needs include large-scale representative community studies of HBV, HDV and HCV seroprevalence, assessment of children following introduction of the HBV vaccine in 2002, prevalence estimates of viral hepatitis among individuals with cirrhosis and HCC and data on HCV prevalence using PCR confirmation, to support a viral hepatitis strategy for Malawi