Meeting minutes
Minutes: Formation of a Consortium on Invasive Bacterial
Disease Burden with Focus on Invasive Salmonelloses in subSaharan Africa, 24 January 2009, Kilifi, Kenya
To review current published and unpublished data and discuss the way forward for defining
the burden of invasive Salmonella in sub-Saharan Africa, 28 investigators from 14 research
sites in sub-Saharan Africa and five international institutions met on 24 January 2009 in Kilifi,
Kenya. The conference was convened by the International Vaccine Institute (Seoul, Republic
of Korea) and co-hosted by the Kenya Medical Research Institute (Kilifi, Kenya).
Meeting participants:
Katrin Kösters (Albert Schweitzer Hospital, Medical Research Unit, Lambaréné, Gabon)
Jürgen May (Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany)
Robert F. Breiman (CDC Kenya, Nairobi, Kenya)
John A. Crump (Duke University - Kilimanjaro Christian Medical Centre Collaboration, Moshi,
Tanzania)
John Clemens, Michael Favorov, Florian Marks, and R. Leon Ochiai, (International Vaccine Institute,
Seoul, Korea)
Kamala Thriemer (International Vaccine Institute, Pemba, Tanzania)
Lorenz von Seidlein (International Vaccine Institute, Zanzibar, Tanzania)
Sam Kariuki (Kenya Medical Research Institute, Nairobi, Kenya)
Kevin Marsh, and Susan C. Morpeth (Kenya Medical Research Institute - Wellcome Research
Programme, Kilifi, Kenya)
Yaw Adu-Sarkodie (Kwame Nkrumah University of Science and Technology School of Medical
Sciences, Kumasi, Ghana)
Denise Dekker (Joint Malaria Program - London School of Hygiene and Tropical Medicine, Korogwe,
Tanzania)
Hugh Reyburn (Joint Malaria Program - London School of Hygiene and Tropical Medicine, Moshi,
Tanzania)
Robert Heyderman (Malawi - Liverpool - Wellcome Trust Clinical Research Programme, Blantyre,
Malawi)
Usman Nurudeen Ikumpayi (Medical Research Council Laboratories, Basse, The Gambia)
Stephen Obaro (Michigan State University, East Lansing, USA)
George Mtove (National Institute of Medical Research, Amani, Tanzania)
Saidi M Ali and Shaali Ame (Public Health Laboratory – Ivo de Carneiro, Pemba, Tanzania)
Gordon Dougan (Sanger Institute, Cambridge, UK)
John Wain (Health Protection Agency, London, UK)
Karen H. Keddy (National Institute of Communicable Diseases, Johannesburg, South Africa)
Ben Amos (Teule Hospital, Muheza, Tanzania)
Myron M. Levine (Center for Vaccine Development - Bamako, Mali)
William Mwengee (World Health Organization Tanzania Office, Dar Es Salaam, Tanzania)
Laura Martin (Novartis Vaccine Institute for Global Health, Italy), Observer
Moses Mwangi, (Sanofi Pasteur, Kenya), Observer
Meeting minutes
Agenda:
Opening speech – Dr. Sam Kariuki
Presentation on IVI – Dr. John Clemens
Introduction and presentation of sites
Ghana – Dr. Yaw Adu-Sarkodie
Nigeria – Dr. Stephen Obaro
Gabon – Dr. Katrin Kösters
Tanzania (Muheza) – Dr. George Mtove
Tanzania (Moshi) – Dr. John Crump
Zanzibar (Pemba) – Dr. Shaali Ame / Dr. Kamala Thriemer
Kenya (Nairobi) – Dr. Robert Breiman
Malawi – Dr. Robert Heyderman
South Africa – Dr. Karen Keddy
Mali – Dr. Myron Levine
Kenya (Kilifi) – Prof. Dr. Kevin Marsh
Presentation – Dr. Gordon Dougan
Genetic variability of Salmonella enterica and challenges in
diagnostics for typhoid fever
Presentation – Mr. Leon Ochiai
The DOMI experience: Lessons learned from a five-country,
standardized disease burden study of typhoid in Asia
Presentation – Dr. Lorenz von Seidlein
Presentation of a draft consortium protocol followed by discussion
Meeting resolutions – Dr. John Clemens / Dr. Sam Kariuki
A) Opening speech by Dr. Sam Kariuki / KEMRI
Dr. Sam Kariuki presented data on several typhoid fever (TF) outbreaks in Kenya and data on
antimicrobial drug resistance of isolates. Prior to 1992, the majority of bacterial isolates were
susceptible to antimicrobial compounds; after 1992, resistance spread quickly, thereby
rendering >80% of S. Typhi strains resistant against mainline antimicrobials. In addition, Dr.
Kariuki described problems in diagnosis, as appropriate isolation of S. Typhi from blood, bone
marrow or CSF is expensive and not widely available in Kenya. Outbreaks can be expected in
the future since health services cannot be delivered to resource-poor settings where the
population is increasing. He concluded that effective, standardized surveillance is crucial at a
national level and that vaccinations might become a viable option in sub-Saharan countries
due to increasing levels of MDR.
B) Presentation of the IVI by Dr. John Clemens / IVI
Dr. Clemens described the IVI, which is a center of excellence in vaccine sciences. During his
presentation, he presented the IVI’s Diseases of the Most Impoverished (DOMI) Program and
its multi-country program on typhoid fever, which was based on standardized surveillance
methods in participating sites in Asia. He also presented data from African sites with which IVI
is currently collaborating, highlighting the need for standardized surveillance in sub-Saharan
countries.
Meeting minutes
C) Presentation of Ghana site by Dr. Yaw Adu-Sarkodie / KCCR
Dr. Yaw Adu-Sarkodie described the study site in Agogo, Ghana, which is a rural village 80
km northeast of Kumasi, the second largest metropolitan area in the country. The study
hospital is the Agogo Presbyterian Hospital, the oldest mission hospital in Ghana with a
catchment population of about 70,000 people. Passive, hospital-based surveillance for febrile
illnesses commenced in 2006, and all patients with acute fever or history of fever (for the past
three days) who required hospitalization were enrolled in the surveillance study. Malaria
slides and blood cultures were prepared for disease diagnosis. Initial results revealed high
incidences of S. Typhi (around 205/100,000 among 4-5 year olds) and of Non-Typhoid
Salmonella (NTS) (around 1,650/100,000 among 1-2 year olds). MDR strains of S. Typhi and
NTS were found although ceftriaxone and ciprofloxacin remain effective.
D) Presentation of Nigeria site by Dr. Stephen Obaro / Michigan State University
Dr. Stephen Obaro described the CABSYNC study (Community-Acquired Bacteraemic
Syndrome in Young Nigerian Children) that is on-going. Study sites include the National
Hospital, Zankli Medical Center and Nyanya Health Center, which cover parts of rural areas
and parts of urban areas. The study will utilize an automated blood culture system and is
aimed at defining etiology of febrile illnesses in children between 2 months to 5 years of age.
Participants are evaluated for malaria with a blood smear, blood culture and HIV-testing. This
study commenced enrolment in November ’08. A brief summary of another study which has
just concluded from Ibadan, Southwestern Nigeria was also presented. This study utilized
traditional culture system and 1,210 children were enrolled with 27 children diagnosed with
invasive disease from Salmonella species.
E) Presentation of Gabon site by Dr. Katrin Kösters / Albert Schweitzer Hospital
Dr. Kösters described the rural study site in Lambaréné, Gabon. The Albert Schweitzer
Hospital (ASH) was founded in 1913 and is run by the International Albert Schweitzer
Foundation in cooperation with the Ministry of Health of Gabon. It has a catchment population
of 50,000; in 2007, 5500 patients were admitted and 24,500 patients were seen at outpatient
clinics. The adjacent Medical Research Unit (MRU), which is run by the University of
Tübingen, Germany, works particularly on Plasmodium falciparum malaria, tuberculosis and
schistosomiasis, and more recently, also on bacteria. The bacteriological lab was set-up in
2008. Among the 400 specimens from all age groups that have been blood-cultured to date,
one S. Typhi specimen and three NTS specimens, all fully susceptible, were isolated.
F) Presentation of Muheza, Tanzania site by Dr. George Mtove / NIMR
Dr. George Mtove presented data from the Teule Hospital in Muheza, Tanzania. Children
between 2 months and 14 years of age were enrolled and the hospital serves a rural
catchment area of 277,000 people. Among 5,031 enrolled children, 23 S. Typhi cases and
205 NTS cases were detected. The first 161 NTS isolates were sero-typed and the following
was found: 137 (85%) S. Typhimurium, 11 (7%) S. Enteritidis, 6 (4%) S. Dublin, 1 (0,7%) S.
Hvittingfoss, and 1 (0.7%) S. Heidelberg. In addition, risk factors were presented; recent
malaria infection and age <5 years were associated with increased risk for NTS infection.
G) Presentation of Moshi, Tanzania site by Dr. John Crump / KCMC
Dr. Crump presented data from the site in Moshi, which were obtained from the Kilimanjaro
Christian Medical Centre and Mawenzi Regional Hospital. Fever surveillance began at this
rural site in July 2006 and patients older than two months of age admitted to the hospital in
Moshi with acute fever or history of fever were enrolled in the study. Blood for malaria slides
and blood culture were obtained from patients, and within one year, 411 adults and
adolescents were enrolled, among which 10.5% died. In 19.3% of cases, pathogens could be
isolated from blood culture. Among these, 36.1% were S. Typhi and only 1.4% were NTS,
which is in sharp contrast to data presented from the Muheza, Tanzania, site 300 kilometers
to the east. 480 children were enrolled during a similar time period, among which 7.5% died.
Meeting minutes
In only 4% of cases, pathogens could be isolated through blood culture. The major pathogen
was Streptococcus pneumoniae (33.3%), followed by S. Typhi (27.8%). No NTS was isolated.
Additional data on antimicrobial resistance was presented, with the majority of S. Typhi
strains being resistant to ampicillin, chloramphenicol, sulfamethoxazole and trimethoprim but
still susceptible to nalidixic acid and ceftriaxone.
H) Presentation of Pemba, Tanzania site by Dr. Kamala Thriemer / IVI
Dr. Thriemer presented the site at Pemba, a rural island on the coast of Tanzania.
Surveillance has been initiated at the Chake-Chake Hospital and all patients older than two
months of age with acute or reported fever are enrolled. Blood samples are obtained from
patients for blood culture and malaria slides. To date, 1,949 patients have been screened and
146 patients have been enrolled. Ten cultures yielded bacterial growth, which included one S.
Typhi isolate and one NTS isolate. Additional hospitals will be included in the surveillance in
the forthcoming months.
I) Presentation of Nairobi, Kenya site by Dr. Robert Breiman / CDC-KEMRI
Dr. Breiman presented a population-based surveillance approach for 55,000 people in two
sites (rural – 25,000 and urban (Kibera) – 30,000). Every household was visited every two
weeks to detect pneumonia, diarrhea, fever, and jaundice. Obtained blood specimens were
used for blood culture, stored serum and malaria slides. In Kibera, 81 S. Typhi cases could be
detected in cultures from 1,615 blood cultures, with the majority of cases in the age group 5-9
years, yielding a crude incidence of 537/100,000 in this age group. In addition, Dr Breiman
presented an approach to calculate underreporting of S. Typhi using multipliers.
J) Presentation of Malawi site by Dr. Robert Heyderman / MLW
Dr. Heyderman described the research on febrile diseases conducted in Blantyre, Malawi.
The mortality among children under five years in this setting is high (134/1000), and in 2007
1,548 positive blood cultures were detected from 4,275 processed pediatric blood samples
(including contaminants). Among these, there were 266 Salmonella isolates. 4,919 blood
cultures of adult patients were processed and yielded 1,099 positive cultures (including
contaminants). 311 Salmonella isolates were found. In addition, Dr Heyderman presented
data on epidemics of invasive NTS serovars in Malawi.
K) Presentation of South African site by Dr. Karen Keddy / NIED
Dr Keddy presented data from South Africa, where national laboratory-based surveillance for
nine bacterial and fungal diseases is being conducted in 170 clinical microbiology
laboratories. All patients are included in the surveillance program. Annually, between 1,400
and 1,600 Salmonella isolates are collected, and the majority of isolates are S. typhimurium
(ca. 60%). S. Typhi isolates are about 15% of isolates.
L) Presentation of Mali site by Dr. Myron Levine / CVD – Mali
Dr. Levine showed data from Mali, a land-locked country with a high infant mortality rate of
>135/1,000. Surveillance is conducted at the Hopital Gabriel Touré (HGT) and all children (015 years) with fever >39.0°C, and signs and symptoms suggestive of invasive bacterial
disease are enrolled. They identified 519 NTS isolates, among which 365 were from inpatients, and 135 cases of S. Typhi were diagnosed. In addition, case fatality rates (CFR) of
NTS and of S. Typhi in in-patients were presented, with the highest rates in highest in children
<12 months old (29% and 37,5%, respectively). Dr. Levine presented data on drug
susceptibility to commonly used antimicrobials, and indicated the existence of high resistance
in S. enteritidis and typhimurium isolates against ampicillin, choramphenicol, trimethoprimsulfamethoxazole but almost no resistance in S. Typhi isolates against these compounds.
Meeting minutes
M) Presentation of Kilifi, Kenya site by Prof. Dr. Kevin Marsh / KEMRI
Surveillance for bacteremia began in 1998, and more than 50,000 patients have been
enrolled in the course of the study. No S. Typhi isolates could be detected during the study.
The incidences of NTS infection were about 170/100,000 in under two year olds and
88/100,000 in under five year olds. The majority of NTS serotypes were S. Typhimurium
(52%) and S. Enteritidis (38%). In addition, Prof. Marsh demonstrated a decline in NTS, which
was in parallel with a decline in P. falciparum malaria incidence.
N) Presentation on genetic variability of Salmonella isolates by Dr. Gordon Dougan /
Sanger Institute
Dr. Dougan described the advantages of a genome-wide scan of Salmonella isolates. This
would provide a unique identification of various strains and enable researchers to assess not
only the geographic origin but also progenitor strains of particular haplotypes. A phylogenetic
tree of all haplotypes could be constructed as each lineage is composed of a different genetic
combination.
O) The DOMI experience by Mr. Leon Ochiai / IVI
Mr. Leon Ochiai described the DOMI (Diseases of the Most Impoverished) Program
conducted in Asia. The program was a multi-centric, multi-disciplinary program coordinated
by the International Vaccine Institute. At the initiation of the DOMI Program, limited
population-based data on typhoid was available and existing incidence data did not allow for
cross-country comparisons, and thus a standardized study design was implemented to obtain
comprehensive and comparable population-based data. The program also conducted
standardized policymaker surveys, economic, and socio-behavioral studies. Summaries of
the cross-country study results on incidence, antibiotics resistance, cost-of-illness, and costeffectiveness studies were presented. It was suggested that multi-centric, multi-disciplinary
studies are critical in assessing burden of invasive salmonelloses in Africa, and that
population-based data can be enhanced by inclusion of socio-behavioral and economic
studies for informing global policy on intervention for these diseases. Mr. Ochiai concluded
that the DOMI Program illustrated the feasibility of such multi-centric, multi-disciplinary
approach.
P) Presentation of draft consortium protocol for discussion by Dr. Lorenz von Seidlein
/ IVI
Data derived from the various presentations of meeting participants were difficult to compare,
underlining the need for standardized febrile illness surveillance. Dr. Lorenz von Seidlein
presented a draft protocol for the conduct of standardized surveillance in participating
countries. The details and results of the discussion are in Appendix 1.
Q) Meeting resolutions by Dr. Sam Kariuki / Dr. John Clemens
The conference ended with the conclusion that existing epidemiological information on
invasive salmonelloses in sub-Saharan Africa is still fragmentary, and hindered by
heterogeneous study methodology. It was agreed among the participants that there is an
urgent need to collect better data on invasive Salmonella infections in sub-Saharan Africa.
Collection of standardized, multi-country, multi-disciplinary data on the burden, risk factors,
and costs of these infections will be essential to help develop a consensus at the regional,
national, and international levels in establishing appropriate control measures. The optimal
method is to utilize existing fever surveillance studies but to standardize epidemiologic and
laboratory procedures across sites. Additionally, vaccine demonstration projects should be
considered for sites with known high burden of typhoid fever such as the urban slums of
Nairobi, Kenya.
Dr. Sam Kariuki and Dr. John Clemens presented the meeting resolutions. The participants
agreed upon the creation of an African salmonelloses initiative for epidemiological research
and advocacy. This new consortium will mount much-needed standardized multi-country
Meeting minutes
studies to yield evidence about the disease burden of typhoid and other invasive
salmonelloses and the effectiveness of typhoid vaccines in sub-Saharan Africa, which can
ultimately lead to the systematic deployment of interventions against invasive Salmonella
infections. It was discussed that these studies could also generate research and research
training opportunities for young African scientists. The IVI’s DOMI Program, which was
described earlier, could serve as a blueprint for the set-up and conduct of such concerted
collaborative action.
The IVI was chosen to act as the secretariat of the consortium and to coordinate consortium
activities, as well as bi-annual consortium meetings. The steering group for the consortium is
yet to be determined. In addition, the group agreed upon the development of a Letter of Intent
that will be reviewed and approved by consortium members, and will be jointly submitted to
the Bill and Melinda Gates Foundation for funding.
Appendix 1
Results of the technical discussion of the draft protocol presented by Dr. Lorenz von
Seidlein (IVI)
Site selection (see table below for sites currently planning to participate)
o Looking at the map at early stage to find out “gaps”
 Consider approaching Francophone countries
 Consider looking at other networks (e.g. RTSS, PneumoNET, etc.; since
they will have the infrastructure already)
Standard protocol across sites
• Both epidemiologic and laboratory
• To compare and contrast results (differences across sites may not be ascribed to
differences in procedures)
• To combine data for analysis for robust findings
Study design - Overview
• Prospective cohort study in a standardized fashion
• Enroll febrile children and adults
– Standardized clinical and epidemiologic information will be collected
– Specimens will be obtained for a standard aerobic blood culture, a malaria
slide, and an HIV antibody test
– Acute sera will be archived
– In-patient discharge outcome will be documented
– Follow-up for sequelae and mortality after discharge
– Case-control studies of risk factors
• Private and public costs of invasive Salmonella and other bacterial infections
• Social science studies on perceptions and health seeking behaviour for febrile
illnesses
• Studies of policy makers views of Salmonella and Salmonella control
• Planning of interventions to control Salmonella in Africa
• Population based study will be robust, but will depend on the funding and site
characteristics
– Catchment area should be well-defined - for calculation of incidence data
– Different approaches by site possible
– If hospital-based, mapping of patients and data from National Mapping
Service to get good catchment areas will be important.
Study population
• Enroll individuals from a catchment area with:
– All ages?
– Neonates should be included since they are the ones at risk from NTS
• Drawing blood from neonates may require skilled technicians, but it
should not be discouraged since it provides important information for
clinical care
• One possibility would be the inclusion of neonates after initial
investigational procedures have been established
– Fever
• History of fever of 3 days or more?
• Definition fever: could be history, could be 37.5C axillary?
• We should not only look for febrile cases, especially for infants
– HIV testing according to regulation of each participating country
– -> Potential ethical issue: HIV counselling & treatment?
– -> There has to be resources to treat HIV if detected
– -> sometimes IRB can ask for higher standard of treatment in a research
scenario
Methods
• Standardized data will be important, but most sites may have their own data
collection system already
Appendix 1
Consortium should focus on “data extraction” system instead of making a
new case report form
Provide clinical assessment and treatment according to WHO/national guidelines
Obtain written informed consent
Assign a unique surveillance code number to identify all documents and laboratory
specimens (i.e., no personal identifiers like names)
Complete a standard case report form
For discussion: Obtain elemental clinical data on admission to develop of scales for
diagnosis and prognosis?
•
•
•
•
•
•
o
•
•
•
•
•
•
•
Scoring system based on a set of definitions on clinical scales can be applied to
determine its validity
 Need to develop core-agreed (“consortium-agreed”) set of definitions of
clinical scales
 Such was often tested for mortality, but not so much for diagnosis – may
be difficult to come to a set of definitions, but may worth trying
Point-of-care testing, as indicated
• RDT for P. falciparum
• Heamoglobin
• Blood glucose
Standard aerobic blood culture (Bactalert / BacTec)
• 5–10 ml of blood from adults inoculated into culture bottles
• 1–3 ml of blood from infants and children inoculated into paediatric culture
bottles
Malaria slide (thin and thick films) – single read according to standard methods
HIV testing
• 2 ELISA tests
• PCR for discordant results and for specimens from those <18 months of age
• Viral load / CD4 count
Sera for archiving
Capture in-hospital outcome
Follow-up at 4 weeks (from initial presentation) for:
• Treatment compliance
• Disability
• Carriage?
o
•
Follow-up of patients may depend on the site setting – some sites may not
have access to individual household to follow up
 This could be applicable to some sites, but not to all sites
 Follow-up after 4 weeks (from initial presentation) for treatment
compliance and disability
 For those places with capability to do so (ones with DSS), looking
into carriage after 12 months is essential
 For all sites (regardless of the capacity to do repeated follow up of
cases), at least mortality survey should be done
Long-term follow-up to assess disease outcomes: 3, 6, 12 months?
Laboratory capacity
• Incubating and monitoring blood culture bottles according to standardized methods
(BacTec or BactAlert), For culture, BACTEC or BacTAlert should be acceptable as
they give same results (John Crump)
• Isolating Salmonella and other pathogenic bacteria from blood
• Identifying common bacteria to the species level
• Antimicrobial resistance profile
• Archiving bacterial isolates
• Reading malaria films
• HIV testing
• Processing and storing sera at -80ºC,
• Shipping samples to reference laboratories
Appendix 1
•
•
•
•
•
•
Blood volume – more is always better, but that is not feasible all the time
• Measure the culture bottle before and after to record the actual volume taken
Put centralized QC system in place
Some sites may want to look into more than salmonella…
• The consortium protocol will be a skeleton specifically focusing on
salmonelloses and possibly other aerobic organism, and each site could add
on to it what they are doing or interested in doing
Provision of training is essential
Reference lab can be more than one
Put in consideration from the initial stage the transfer of shipments
• Usually with the “WHO reference lab” as the addressee, transportation of the
specimens is not a problem
Reference laboratories
– Receive isolates from participating laboratories
– Providing QC/QA and training
– Antimicrobial susceptibility testing to a recognized international standard (e.g.,
Clinical Laboratory Standards Institute)
– Serotyping Salmonella
– HIV PCR / viral load
– Regional reference laboratories could be established
– Selection of reference laboratories should be fair and transparent
– Microbiological task force must work out problems for proficiency testing
Collaborating laboratories
• Receive samples from participating laboratories
• Evaluating diagnostic tests (e.g., new RDTs)
• Conducting basic science research relevant to vaccine development
 Include microbiology and genotyping issues (Sanger, Bernhard Nocht Institute for
Tropical Medicine)
Nested studies
• Case-control studies
– To assess risk factors (demographic, geographic, water - sanitation, socioeconomic characteristics, and animal husbandry) for S. Typhi, NTS, and
other bacterial bloodstream infections,
– Method: sex and age-group matched





•
General comment – many studies have already been conducted and
some of these nested studies should be optional by site
 Though it is possible to give freedoms to each site, but not
insisting on standardized model will lose attractiveness to donors
Case-control study can have two aims:
o 1) look into co-morbidity, and
o 2) source of infection
Some sites have already done their risk assessment – they may look into
the forms and consider use of the same one for other sites
Considering investigations in veterinary source might be worth
Economic and socio-behavioral studies have been carried out in many
places, but often not interpretable or out of context
 It is essential to have appropriate specialist leading these studies
and an attractive proposal for the donor
Economic studies
– Private costs-of-illness
• sample by age-group (infants/children/adults)
• inpatient vs. outpatient
• Interview on consultation/admission and during the 4-week follow-up
– Public costs – including capital and running costs
Appendix 1
•
Socio-behavioural science studies
– On perceptions of disease, health seeking behaviour for febrile illnesses and
demand for control/intervention:
• Qualitative rapid assessments of 5-10 community leaders and 5-10
health care workers (convenience sampling)
• Quantitative survey of community members (existing census data
used to randomly select 300 to 400 adult community members)
• HUS questions also included in CRF
•
Vaccine demonstration projects
– To demonstrate mass typhoid vaccination in known high disease burden
sites
– To assess vaccine’s impact in reducing typhoid fever
– To assess feasibility of mass typhoid vaccination
•
Interview policymakers on their views of bacterial infections specifically Salmonella
(in an era of malaria elimination, potential control of Pneumococcal and H.flu
infections through vaccination).
Plan
•
•
•
•
Identify potential donors
Submit LOI
Develop full proposal
Once funded, implementation will occur in several phases:
Implementation phases
• Phase I: Site establishment
– Develop standardized protocols for all studies
– Develop and standardize laboratory methods, train clinical research staff.
• Phase II: Surveillance
– Sites will establish and sustain surveillance for invasive Salmonella and other
bacterial infections.
• Phase III: Reference laboratories
– Reference laboratories will receive samples for antimicrobial susceptibility
testing, Salmonella serotyping, evaluating diagnostic tests, and conducting
basic science research relevant to NTS vaccine development.
• Phase IV: Special studies. Sites will conduct nested special studies.
• Phase V: Vaccine demonstration project or pilot introduction should be considered as
final phase for sites with enough data on typhoid
Discussion
 Potential donors
o The consortium will aim to approach Gates/Wellcome
 Organization
o Coordinating role will be by the IVI (Secretariat/management role)
o Governance should be by selected individuals/institutions of the consortium
possibly in rotating fashion
Appendix 2
Table 1: Summary of presentation of participating sites and remarks during discussion
Location
Type
location
Type surveillance
Inclusion criteria
(fever etc.)
Age group
Lab tests
Remarks
Agogo
(Ghana)
Rural
Hospital-based,
passive
History (72h) or
acute fever and
severe disease
>2 months
Blood culture
(BC), malaria
- high proportion of culture-positive (about 20%)
- Sensitivity testing for Nalidixic acid not done
Kilifi
(Kenya)
Rural
Hospital-based,
passive
All pediatric
admissions
Pediatric
populations
BC, HIV,
malaria
- Malaria and NTS declining along the Kenyan coast
(parasitemia rates proportional to NTS rates)
Bamako
(Mali)
Urban and Hospital-based,
rural
passive
0-15y
BC, malaria
71% of admission presumed infection. 50% of them
malaria. In 6 years (2002-2008) 519 NTS (365 from
inpatients) cases and 135 S. Typhi cases. 84.4%
from Bamako residents
Lambaréné
(Gabon)
Rural
Hospital-based,
passive
Muheza
(Tanzania)
Rural
Hospital-based,
passive
Fever >39°C,
Clinical syndrome
suggestive of
invasive bacterial
disease
Any febrile illness
suspicious of
invasive bacterial
infection
History (72h) or
acute fever and
severe disease
Moshi
(Tanzania)
Urban
and
rural
Hospital-based,
passive
Nairobi
(Kenya)
Urban
All age-groups BC, HIV,
(at physicians malaria
request)
- S. Typhi and NTS isolated from children over 9
years adult population
2 months to 14 BC, HIV,
years
malaria
- Unrelated and sporadic occurrence of S. Typhi
Pediatric: History > 2 months
(72h) or acute
fever and severe
disease
Adult: >38.0°C
(oral)
Active, population-based >38.5C and/or
all
(defined denominator)
patients suspected
with household based and of severe
clinic based surveillance pneumonia
BC, HIV,
malaria
- no NTS found among children, 1 NTS in adult
group
- high percentage of S. Typhi infections (36 S. Typhi
in 90 positive cultures)
- no Nalidixic acid resistance found
BC, malaria,
HIV, NP/OP
swabs on
patients
meeting
pneumonia or
influenza
- HUS showed 39% of fever cases and 47% of
diarrhea cases seeking care at pharmacies
- High incidence of typhoid (400/100,000 py) among
5-9 yo
- NTS and S. Typhi much higher in urban population
- 2 strains resistant to ciprofloxacin, 8 strains
resistant to Nalidixic acid
Appendix 2
criteria
Pemba
(Zanzibar)
Rural
Hospital-based
Passive
3 days or more
> 2 months
blood culture,
HIV, malaria
Urban and Hospital based
Rural
Passive
Less than 14days 2-59mo
(Nigeria)
Blood culture
Malaria, HIV,
APR
38% national immunization coverage, some states
< 10%. High rates of non-prescribed antibiotics use.
Blantyre
(Malawi)
Urban &
Hospital-based
Rural Sites Passive
Any febrile illness Few neonates;
(not Malaria)/
largely >2mths
suspicious of
invasive bacterial
infection
266 Salmonella, 95% S. enterica. Two NTS
epidemics (1 from enteritidis, Dec 98 – Dec 02),
drug resistant, 1 from typhimurium (end of 02),
sensitive
(S. Africa)
Countrywide
N/A – all
invasive/noninvasive
Salmonella
blood culture,
CSF, HIV,
malaria,
radiology,
sputum smear
& culture
Specimen
culture
Active laboratory
surveillance
All ages
Active laboratory-based system. Surveillance
officers at 10 sites around the country collect clinical
information. About 170 labs countrywide submit
data (CRF and isolates) to the NICD.
Predominantly S. typhimurium, some enteritidis,
some S. Typhi. Majority of S. cases are HIV+;
Patient outcome: Death rate very high, 30%