Review Article

Global Epidemiology of Invasive Haemophilus influenzae Type a Disease: Do We Need a New Vaccine?

Table 1

Geography of reported cases of invasive Hia disease#.
(a) U.S.A.* (excluding Alaska)

Geographic area/populationTimeNumber of reported invasive Hia isolatesAverage annual incidence per 100,000 populationCommentsReference

White Mountain Apache
(east and central Arizona)
Oct 1981–Jan 19833 out of 18 cases of invasive H. influenzae diseaseNot reportedProspective surveillanceLosonsky et al., 1984 [12]

Metropolitan Atlanta1983–19855 out of 310 invasive H. influenzae isolates from all hospitals in the greater Atlanta areaNot reported2-year survey of invasive H. influenzae diseaseElliott et al., 1990 [21]

California, New Jersey, Tennessee, Oklahoma, Missouri, Washington (population 33.5 million)Jan–Dec 198614 out of 1872 invasive H. influenzae isolates (0.7%)0.04Laboratory-based surveillance during time when Hib polysaccharide vaccines were being introducedWenger et al., 1992 [22]

San Francisco county1989–19911 out of 12 invasive H. influenzae isolates from adults with HIV infectionNot reportedPopulation-based, 3-year active surveillanceSteinhart et al., 1992 [23]

Navajo and White Mountain Apache children <5 years (northern and central Arizona, western New Mexico, southern Utah)1988–200376 cases out of 378 invasive H. influenzae isolates20.2 for children <5 years; no increase in rates after Hib vaccination was introducedPopulation-based, active laboratory surveillance data Millar et al., 2005 [24]

4 states (Georgia, Tennessee, Maryland, California); population > 10 million1994–19952 cases of Hia out of 18 H. influenzae meningitisNot reportedActive, population-based surveillanceSchuchat et al., 1997 [25]

Illinois1996–20048 Hia out of 475 H. influenzae (4/8 in <5 years old)Not reportedRetrospective analysis of surveillance dataDworkin et al., 2007 [7]

Utah children <18 years old1998–2008Hia: most prevalent serotype
22 cases/91 invasive H. influenzae disease
28% of cases in children <5 years old
In 1998: 0.8 for children
In 2008: increased to 2.6
Population-based study
In Utah, no Hia in 1991–1998, in 1998-1999: 5 pediatric cases in 10 months, then increased incidence between 1998 and 2008
Bender et al., 2010 [26]

Utah adults1998–2008Hia 15/1010.08 for adults; no annual changesPopulation-based studyRubach et al., 2011 [27]

ABCs (California, Connecticut, Colorado, Georgia, Maryland, Minnesota, New Mexico, Oregon, New York, and Tennessee (11.7% of the US population in 2008)1999–2008Hia: 92 (2.2%) of all invasive isolatesNot reportedActive population- and laboratory-based surveillance conducted through Active Bacterial Core surveillance (ABCs) sites
Hia: more frequent cause of invasive disease in American Indian and Alaska Native children compared with nonnative children
MacNeil et al., 2011 [28]

New Mexico2009-2010Cluster of 5 cases in 2009; 7 more sporadic cases in 2009-2010Not reportedABCs data posted on the website hosted by the Imperial College (UK)http://haemophilus.mlst.net/ [29]

Hib conjugate vaccine became available in 1988; in 1991, all infants starting at age of 2 months were recommended to receive the vaccine [30].
(b) Alaska and Canada**

Geographic area/populationTimeNumber of reported invasive Hia isolates Average annual incidence per 100,000 populationCommentsReference

Alaska residents aged 10 years and older1980–19962/17 of non-type b serotypeable strainsNot reportedPopulation-based, descriptive correlational studyPerdue et al., 2000 [31]

IMPACT
12 Canadian pediatric tertiary care centers: nearly 90% of tertiary care pediatric beds in Canada (population 3 million children)
1996–200125/166 of invasive H. influenzae isolates from children; 76% of patients with Hia: AboriginalIn the Keewatin Region of Nunavut (2001): 418.8 for Inuit children <5 years; in British Columbia, Alberta, Manitoba, Saskatchewan (1996–2001): 3.7 for Aboriginal children <5 years; 2.3 for Non-Aboriginal children <5 yearsRetrospective population-based studyMcConnell et al., 2007 [8]

Manitoba2000–200426/52 (50%) of invasive H. influenzae isolatesNot reportedLaboratory-based surveillance Tsang et al., 2006 [32]

Manitoba2000–200636/122 (29%) of invasive H. influenzae isolates; 72% of Hia cases: children <2 years0.26 (2000), 0.69 (2001), 0.51 (2002, 2003), 0.34 (2004), 0.59 (2005), 0.16 (2006)Laboratory-based surveillanceTsang et al., 2007 [33]

Alaska and northern Canada2000–200542/88 of typeable H. influenzae isolates0.9 (Alaska: 0.3, northern Canada 3.9); 19.7 for children <2 years (Alaska: 5.7, northern Canada: 79.1); 52.6 for indigenous children <2 years (Alaska: 20.9, northern Canada: 101.9) Population-based surveillanceBruce et al., 2008 [34]

Northern Canada (Yukon, northwestern territories, Nunavut, northern Quebec, and Labrador): population 132,956; 59% Aboriginal2000–200531/59 (59%) cases of invasive H. influenzae disease with serotype information; 73.3% of these in children < 2 years Not reportedPopulation-based surveillance, all Hia cases occurred in Aboriginal personsDegani et al., 2008 [35]

Ontario1989–20072.1% of 1,455 of invasive H. influenzae isolates
8/284 (2.8%) in children < 2 years; 6/160 (3.75%) in children of 2-10 years
Not reportedPopulation-based surveillanceAdam et al., 2010 [6]

Northwestern Ontario (20% Aboriginal population)2002–200813/31 (41.9%) of invasive H. influenzae isolates with serotype informationFor children < 5 years: 7.7 (2002, 2003, 2008), 15.5 (2006), 23.2 (2004)Population-based surveillanceBrown et al., 2009 [36]

Northwestern Ontario (82% Aboriginal population)2004–20087 cases in First Nations communities 7.0Population-based surveillanceKelly et al., 2011 [37]

British Columbia2008–200910% of 98 invasive H. influenzae isolates; 80% (8/10) in children <2 yearsNot reportedRetrospective laboratory surveillance studyShuel et al., 2010 [38]

Northern Canada2000–201072 (56% of cases with serotype information) out of 142 invasive H. influenzae cases4.6 (average incidence over 11 years); 87.5 for children <2 years; 6.9 for Aboriginal people Population-based surveillanceLourenco et al., 2012 [39]

In Canada, the first Hib conjugate vaccine became available in 1988 for children older than 18 months of age; the current conjugate vaccine for immunization of infants beginning at 2 months of age was introduced in 1992 [6].
(c) South America

Geographic area/populationTimeNumber of reported invasive Hia isolates Average annual incidence per 100,000 populationCommentsReference

Sao Paulo (Brazil)1977–19915 out of 1,094 isolates from CSF (0.5%); in comparison, Hib was isolated in 99.4% of cases of meningitisNot reportedNational surveillanceLandgraf and Vieira, 1993 [40]

Brazil1990–199916 (0.5%) Hia out of 3,204 invasive isolates (prevaccine) Not reportedRetrospective study;
Hib vaccine was introduced in August 1999
Zanella et al., 2002 [41]

The metropolitan region of Salvador (northeast Brazil)March 1996–September 200013/483 (2.7%) isolates from meningitis. Proportion of Hia cases increased from 5/431 (1.2%) to 8/52 (15.4%) after introduction of routine Hib immunizationPrevaccine 0.02;
Postvaccine: 0.16 (8-fold increase);
In <2 year-old children: increase from 0 to 1.77
Active surveillance for H. Influenzae meningitis cases before and after introduction of Hib immunizationRibeiro et al., 2003 [42]

Metropolitan Salvador, Brazil August 1996–August 200419 out of 25 cases of non-type b
H. influenzae meningitis (76%): 4 cases in the pre- and 15 in the postvaccination period
Increased from 0.01 to 0.14 in the first year after introduction of vaccine; in children <2 years, increased from 0 to 1.56;
during the following 4 years: between 0 and 0.03
Active surveillance for H. influenzae meningitis in childrenRibeiro et al., 2007 [43]

Salvador, BrazilMarch 1996–September 200728/43 (65%) of non-type b
H. influenzae meningitis
Not reportedActive hospital-based surveillance for meningitisLima et al., 2010 [44]

Brazil1990–2008In 1990–1999: 24/3,050 of H. influenzae meningitis isolates (1%)
2000–2008: 118/860 (14%)
Hia meningitis in infants <1 year: 0.31 in 2000–2002; 0.90 in 2003–2005; 1.48 in 2006–2008Passive laboratory surveillance; retrospective analysisZanella et al., 2011 [45]

Cuba 1993–1995Hia 0.6% of all H. influenzae isolates from meningitis (97% Hib)Not reportedNationwide surveillance
Hib conjugate vaccine was introduced in 1999 [46]
Martínez et al., 1999 [47]

Colombia1994–200210/683 invasive H. influenzae isolatesNot reportedLaboratory-based surveillance
Hib conjugate vaccine was introduced in 1998 [46]
Ovalle et al., 2003 [48]

19 Latin American and 4 Caribbean countries 2000–2005131/2,159 (6.1%) invasive H. influenzae isolatesNot reportedLaboratory-based surveillance
Hib vaccine was introduced in Uruguay in 1994, Chile in 1996, Guatemala: 2006, Columbia: 1998 [46]
Gabastou et al., 2008 [49]

(d) Africa

Geographic area/populationTimeNumber of reported invasive Hia isolates Average annual incidence per 100,000 populationCommentsReference

The GambiaDecember 1982–January 19844 out of 55 cases of H. influenzae meningitis; 3 out of 20 H. influenzae pneumoniaNot reportedDetection of IS1016-bexA deletion in the encapsulation (cap) locus of Hia in isolates from 3 casesKroll et al., 1994 [50]

The Gambia1986 (prevaccine)2 out of 13 invasive H. influenzae isolates; 5 more invasive Hia isolates from the same areaNot reportedAnalysis of lung aspirates from 64 patients with acute lobar pneumoniaWall et al., 1986 [11]

South AfricaAug 1991–July 1992 (prevaccine)2 out of 119 invasive H. influenzae isolates from childrenNot reportedOne year prospective study in Cape Town children,
one septicaemia, one meningitis
Hussey et al., 1994 [51]

South AfricaJuly 1999–June 2004 (post-vaccine)10/712 invasive H. influenzae isolates (for comparison: Hif 39/712)Not reportedNational laboratory-based surveillance data,
Hib vaccine was introduced in July 1999
Von Gottberg et al., 2006 [52]

East Africa (Kenya, Uganda, Tanzania, Ethiopia)August 2003–February 200716/119 invasive H. influenzae isolates from children between 2 months and 5 years of ageNot reportedPaediatric Bacterial Meningitis Surveillance Network in the East African Region. Hib vaccine was introduced in Kenya and Uganda in 2001Mudhune and Wamae, 2009
[53]

(e) Papua New Guinea and Australia

Geographical area/populationTimeNumber of reported cases of Hia disease/isolates Incidence rateCommentsReference

Eastern Highlands of Papua New Guinea children <5 years1978–19886.5% (6/92) of blood H. influenzae isolates; 12.3% (9/73) of CSF isolates; 2.9% (1/35) of lung aspiratesNot reportedLaboratory-based surveillance of acute pneumonia and meningitis in childrenGratten and Montgomery, 1991 [54]

Papua New GuineaMarch–December 1986Among 170 adult cases of acute pneumonia, 4/15 of H. influenzae isolates from blood culture or/and lung aspiratesNot reportedProspective study of 170 adult patients with acute pneumoniaBarnes et al., 1987 [55]

Papua New GuineaMarch 1980–September 198412% of H. influenzae isolates from children with meningitis (9 strains)Not reportedStudy of 155 highlands children with bacterial meningitis (2 m–10 y old)Gratten et al., 1985 [10]

Northern Territory (NT), Australiamid 1985–mid 1988 5 out of 80 of serotyped H. influenzae isolate; all from Aboriginal children; one meningitisNot reportedSurvey of all invasive H. influenzae infections over a 3-year period in children under 5 years of age at the NT regional hospitalsHanna, 1990 [15]

Central Australia Aboriginal populationJune 1985–May 1986 2/8 of serotyped H. influenzae from Aboriginal childrenNot reportedPopulation-based surveillanceHansman et al., 1986 [14]

Central Australia Aboriginal childrenMay 1989–February 1993Among 77 children with invasive H. influenzae disease <4 years, 7.5% of episodes were caused by Hia (Hib 79% of the isolates) Not reportedPopulation-based study on Aboriginal children hospitalized with invasive disease in Alice Springs, Tennant Creek and KatherineGratten et al., 1994 [56]

AustraliaJuly 1999–August 20004/200 of invasive H. influenzae isolatesNot reportedStudy of antimicrobial susceptibility of H. influenzae isolated from patients with “clinically relevant” conditions, including invasive and noninvasive. Turnak et al., 2001[57]

Only few prospective population-based studies have been done and most publications present data from convenient samples. Therefore, not all studies report comparable data, such as the incidence rates.