Guidance

Revised recommendations for the prevention of secondary Haemophilus influenzae type b (Hib) disease

Updated 4 September 2024

Summary of changes to the revised recommendations

All confirmed cases of invasive Hib disease and all their household contacts should now be offered antibiotic chemoprophylaxis.

Based on the most recent data from calendar years 2020 to 2022, Hib is not a significant pathogen in any age group. Consequently, the 2024 guidance has been amended to protect those who remain at increased risk, namely the index case and household contacts.

The 2024 guidance no longer includes a definition of ‘Probable Hib’ (previously defined as “individuals with epiglottitis where Hi was isolated from a sterile site”) or a ‘Vulnerable Individual’ in the household (child younger than 10 years or an immunosuppressed or asplenic individual of any age).

Introduction

Haemophilus influenzae type b (Hib) can cause severe life-threatening disease in healthy individuals and is a major global cause of childhood meningitis, pneumonia, epiglottitis, septicaemia, cellulitis, osteomyelitis and septic arthritis (1, 2, 3). It is estimated that Hib causes 3 million cases of serious disease and 700,000 deaths annually worldwide, with case fatality rate of around 5% in high income countries and up to 25% in low-middle income countries (3). The organism can be carried asymptomatically in the naso- and oro-pharynx and acquisition most commonly results from asymptomatic carriers, rather than from cases. Individuals may transfer the organism to close contacts though airborne or droplet spread by coughing and sneezing. In the pre-vaccine era the vast majority (over 80%) of cases occurred in children younger than 5 years of age, with the highest attack rates in those younger than 2 years. The introduction of Hib conjugate vaccine into routine childhood immunisation programmes has initially resulted in a greater than 90% reduction in the incidence of invasive Hib disease, through a combination of direct and indirect (herd immunity) protection (4 to 11). Guidelines for the prevention of secondary cases of Hib in the UK were first published in 1991 (12) and were updated in 1994 after the introduction of the Hib conjugate vaccine into the national infant immunisation schedule in 1992 (13).

In 2009, the UK guidance for the prevention of secondary cases was published (14). The guidance was then updated in 2013 (15). Compared to the general population, close contacts of individuals with invasive Hib disease (particularly in a household or pre-school setting) are at increased risk of developing invasive Hib disease compared with the general population. The greatest risk is the first week after the index case becomes ill, but secondary cases have been reported after this period. At the same time, index cases themselves also have a small but significant risk of a second episode of invasive Hib disease, mainly within 6 months of the initial episode.

In the 2009 guidance, we recommended that index cases aged <10 years should receive rifampicin chemoprophylaxis and the Hib vaccine after they recover from their infection (14). In addition, if there is a vulnerable individual (child <10 years or an immunosuppressed or asplenic individual of any age) among the household contacts of the index case, all members of that household, including the index case, should receive chemoprophylaxis as soon as possible.

Currently, most NHS hospital laboratories do not routinely type invasive H. influenzae (Hi) isolates. Instead, the isolates are usually sent to the UK Health Security Agency (UKHSA) national reference laboratory, resulting in a delay of up to a week before typing results become available. In such cases, or if typing facilities are not available, we developed a definition for ‘Probable Hib’ for the purposes of chemoprophylaxis, which was based on the latest Hib epidemiology at the time (1993 to 2004).

The epidemiology of invasive Hib disease continues to evolve, with very few cases confirmed in any age group over the past decade. The 2024 revision of the 2013 guidance reflects this low risk, with recommendations to offer chemoprophylaxis to the index case and all close contacts of a confirmed case of invasive Hib disease, similar to current recommendations for close contacts of invasive meningococcal disease cases.

Epidemiology

Invasive Hib disease

In the pre-vaccine era, Hib was responsible for almost a thousand cases of invasive infections per year in England and Wales, mostly in children under 5 years of age (16). Over half the cases (57%) presented with meningitis, 14% with epiglottitis, 8% with bacteraemia, 7% with cellulitis and 5% each with bone and joint infections or pneumonin (16). The overall case fatality rate was 4% and was highest in adults over 65 years of age, who often had underlying medical conditions (16). Clinical trials of Hib conjugate vaccines performed prior to licensure demonstrated excellent short-term protection against invasive Hib disease, with efficacy estimates of 83 to 100% (17 to 19). The UK introduced the Hib conjugate vaccine into the infant immunisation programme at 2, 3 and 4 months in October 1992, alongside a catch-up campaign providing one dose of vaccine to children under 4 years of age. This resulted in a dramatic reduction in the incidence of invasive Hib disease in the age group targeted for vaccination, from 21 to 44 per 100,000 in 1991 to 0.63 per 100,000 in 1998. A significant decline in the incidence of Hib was also noted in older children and in adults, most likely due to a reduction in asymptomatic carriage among vaccinated children, which decreased the reservoir for infection, resulting in reduced transmission and herd protection (20, 21).

The rise in the number of cases between 2000 and 2003, particularly in children aged one to 2 years, is considered to have occurred because of a wearing-off of the initial catch-up programme, a greater than expected decline in vaccine effectiveness among children vaccinated in infancy and a temporary change in the diphtheria-tetanus-pertussis-Hib combination vaccine type offered to young infants (4, 22, 23, 24).

During this period, invasive Hib disease in adults also increased to pre-vaccine rates. This increase was associated with a fall in the concentration of serum antibody to Hib in the adult population, indicating reduced immunity among unimmunised adults, possibly due to a reduction in opportunities for natural boosting of immunity to Hib in the vaccine era (20). In 2003, a Hib booster campaign targeting all children aged 6 months to 4 years was introduced and the use of whole cell pertussis DTP-Hib combination vaccine for primary immunisation was resumed (25). In September 2006, a routine booster dose of combined Hib-meningitis C vaccine was introduced into the national infant immunisation programme at the age of 12 months. This was accompanied by a catch-up booster campaign at school entry targeting children who would have been too young for the 2003 booster campaign and too old to receive the scheduled 12-month booster dose (22). The introduction of control measures following the 2000 to 2004 resurgence has led to further reductions in invasive Hib disease across all age groups such that, in 2022, there were only 7 laboratory-confirmed Hib cases (incidence 0.01 per 100,000 population) and none were in children aged <5 years (Table 1).

Hib carriage

Most studies on Hib carriage in the general population were performed in the pre-vaccine era, with reported carriage rates of 0 to 9% (Table 2). Carriage rates were much higher in children compared with adults, although infants were less likely to be carriers than older children (26 to 30). Carriage rates increased with the number of children in the family (29) and with the number of hours spent in day care centres (30, 32 to 35). Following a case of Hib disease, carriage rates were substantially higher among contacts of the index case. Paediatric day care contacts had carriage rates of 10 to 23% (32 to 36) while household contacts had higher carriage rates of 26 to 32% (31, 36 to 39) particularly if the household contacts were children younger than 5 years (carriage rate, 33 to 66%) (31, 34, 36 to 38, 40). Furthermore, family members of children who were colonised with Hib through contact with an index case in a day care centre were also likely to become colonised (31, 37, 38).

Hib conjugate vaccination significantly reduced asymptomatic pharyngeal carriage in both vaccinated and unvaccinated populations (41 to 45). In a serial survey of children aged one to 4 years attending playgroups, nurseries and child welfare clinics in England and Wales, prevalence of carriage fell from 4.0% (95% confidence interval (CI), 3.1 to 5.1%) prior to the introduction of vaccination in 1992 (n=1,531) to 0.70% (95% CI, 0.35 to 1.3%) in 1994 (n=1,563), and 0.0% in 1997 (n=458) and 2002 (n=384) (46). A UK study conducted after the increase in Hib disease reported a Hib carriage rate of 2.1% (95% CI, 0.7-6.0%) among 2 to 4 year old children (n=176) in London (47). In 2005, Hib was isolated from 4.2% of 855 children aged 6 to 16 years recruited from schools in Oxfordshire, while none of 385 healthy adults aged 20 to 40 years were carriers (48). The introduction of the 12-month booster dose of the Hib conjugate vaccine is likely to have a further impact on population carriage of Hib.

Risk of a second episode in the index case

A second episode of invasive Hib disease in the index case is uncommon but recognised (49 to 51) and usually occurs occur within 6 months of the initial episode (50). It is often difficult to distinguish between reinfection and relapse, which can occur even if the index case receives appropriate prophylaxis to eliminate carriage (51). Relapses are associated with poor serum antibody response to the primary infection and persistence of the organism in the pharynx despite treatment (51). Reinfection tends to occur several weeks to months after the primary infection (51, 52). There are limited data on the risk of second episodes in the post-vaccine era. In the UK, only 4 cases with 2 distinct episodes of invasive Hib disease have been identified through enhanced national surveillance during 1992 to 2022. Two cases aged 12 and 77 years were unvaccinated, a 6 year old had received a catch-up dose of Hib vaccine when he developed his second infection and a 7 year old had received 3 doses in infancy and a booster dose after his first episode of Hib at 5 years of age.

Risk of secondary cases

Almost all studies on secondary attack rates for invasive Hib disease were performed in the United States in the pre-vaccine era (53 to 58). Although there were minor differences in the definition of close contact and duration of follow-up, it was possible to statistically combine studies on secondary attack rates in households where contacts had been prospectively monitored for at least 30 days and had not received any chemoprophylaxis (Table 3). On the other hand, studies involving day care centres were found to be heterogeneous and, therefore, are presented separately for each age group (Table 4). These studies demonstrated that household and day care contacts of index cases were at significantly higher risk of developing invasive Hib disease compared with general population (39 to 56). In addition, secondary attack rates generally appear to be lower for day care contacts than household contacts, although statistical analysis was not possible. This observation was most noticeable in 2 studies where there were no secondary cases among 935 and 1,321 day care contacts observed (59 to 60). One retrospective cohort study proposed that the risk of secondary disease is almost negligible if the index case attended the day care facility for less than 18 hours per week or if the contacts attended less than 25 hours per week (61). It should be noted that secondary cases among household and day care contacts can occur up to 11 months after the index case (55 to 58). However, when published studies of secondary cases among household contacts were combined, 44% presented within the first 4 days and 68% within 8 days (54 to 57, 59, 60).

For both household and day care contacts, children younger than 2 years of age (particularly those under one year) were at greatest risk of developing secondary Hib disease, with a very low risk after the age of 4 years. While this observation may be true for the pre-vaccine era, there is no data on secondary attack rates in the post-vaccine era. Based on observations during the recent increase in Hib in the UK, in the absence of good population control, individuals of any age may be susceptible to Hib. It is likely therefore that, as a result of reduced opportunities for natural boosting following mass national immunisation campaigns for Hib (20), and waning of protective antibody levels after infant immunisation (even in children receiving a booster dose of vaccine in the second year of life) (62, 63), a proportion of older children and adults may not be adequately protected against invasive Hib disease (5, 65).

The effectiveness of chemoprophylaxis

Eradication of carriage

Chemoprophylaxis aims to reduce the risk of secondary disease in the index case and among close contacts by eliminating carriage. In randomised controlled trials, rifampicin at a dose of 20 milligrams per kilogram per day (mg/kg/day) for 4 days eradicated pharyngeal carriage of Hib in 92 to 97% of contacts (34, 37 to 40, 65 to 68).

A lower dose of rifampicin at 10 mg/kg/day for 4 days 37 or a shorter 2-day course of 10 mg/kg/day either daily (69) or twice daily (31) were less effective, possibly because of a lower peak antibiotic levels (70). However, one prospective randomised controlled trial comparing a 4-day course of rifampicin (20 mg/kg a day up to a maximum of 600mg) with a 2-day course at the same dose reported similar rates of clearance of Hib pharyngeal colonisation (94% versus 92%) among family contacts, with identical 95% confidence intervals (73 to 99%), although this study was poorly powered, with only 18 and 24 participants in the 2 groups, respectively. Other antibiotics including cotrimoxazole, ampicillin, cefaclor and a single dose of ceftriaxone were less effective than rifampicin (12, 71, 72). The efficacy of ciprofloxacin in eradication of Hib carriage has not been assessed, but has been shown to reach high concentrations in nasal secretions in healthy adults (73).

Eradication of carriage was far more successful in families when all members were treated (97% vs 64%; OR 21.5; 95% CI, 3.0 to 103) (32). However, the efficacy of eradication was significantly lower in children younger than 5 years, the age group at highest risk of secondary disease (31, 38). Furthermore, re-colonisation was very common in this age group, with 22 to 28% of treated carriers re-colonised within one to 4 weeks of rifampicin prophylaxis (37, 38). Rates of new acquisition of Hib among children with negative initial pharyngeal cultures were low and were significantly reduced among those receiving rifampicin prophylaxis compared with placebo for periods of up to one month after prophylaxis (38 to 40).

Eradication of carriage in the index case is also important in order to prevent a second episode of infection and to reduce transmission of the organism to susceptible contacts. Hib carriage can be demonstrated in most index cases before initiating antibiotic therapy (68). Antibiotics such as ampicillin and chloramphenicol that were previously used to treat Hib were not effective in eradicating pharyngeal carriage (39, 74). One prospective study of 38 children with invasive Hib disease reported that the organism was not recovered from throat cultures of any of the children beyond 14 hours after an intravenous antibiotic effective against the infecting Hib isolate (usually a combination of ampicillin with either chloramphenicol, a third generation cephalosporin or nafcillin) was initiated (75). More recently, third-generation intravenous cephalosporins (cefotaxime or ceftriaxone) eradicated carriage in all 53 children with invasive Hib disease after 3 days (76). However, only 9 children were treated with ceftriaxone which is now often the empiric treatment of choice for serious infections in children. In adults, pooled analysis of 4 randomised clinical trials involving 292 patients with acute exacerbation of chronic bronchitis due to H. influenzae reported that treatment with moxifloxacin or macrolides (azithromycin or clarithromycin) reported higher bacterial carriage eradication rates at 7 to 37 days post-infection for moxifloxacin compared with azithromycin (96.8% vs 84.6%, p=0.019) and clarithromycin (90.1% vs 64.2%, p=0.001) (77).

Prevention of second episodes

Eradication of carriage does not always lead to prevention of infection. No prospective trials on the use of rifampicin to prevent second episodes were identified. Cates and colleagues reported that 7 of 9 recurrent cases had received a full course of rifampicin prophylaxis (51). The interval between first and second episodes varied from 9 to 138 days, and the sites of infection were different in the first and second episodes. Six of the 8 recurrent cases that were typed were caused by indistinguishable strains, although it is not possible to determine whether these were relapses or re-infections. All except one case were under 12 months of age.

Prevention of secondary cases

All clinical trials on the use of chemoprophylaxis to prevent secondary cases were performed in the pre-vaccine era (12). Several prospective and retrospective observational studies performed between 1960 and 1986 compared the risk of secondary disease among those who received or did not receive rifampicin (54, 57 to 59, 61, 78). Because these studies reported only a small numbers of secondary cases, results were combined to give overall secondary attack rates in household (Table 5) and day care (Table 6) contacts. Table 6 shows that rifampicin reduces the risk of secondary disease by 94% among day care contacts in the 30 to 60 days following hospitalisation of the index case. Only one trial and none of the observational studies reported attack rates for household contacts (Table 5) and, although only a few children developed secondary Hib disease, none of the 20 secondary cases among household contacts (39, 54, 57, 58) and only one of 19 secondary cases among day care contacts had received rifampicin therapy (39, 59, 61, 78). There have been anecdotal reports of failures of rifampicin prophylaxis among household and day care contacts, usually due to a combination of failure by healthcare professionals to implement rifampicin prophylaxis and poor uptake and compliance by contacts (79 to 81, 37 to 39, 65, 82). Rarely, resistance to rifampicin has been reported (83). Re-colonisation after initial eradication can occur, and it has been suggested that rifampicin prophylaxis merely delays the onset of secondary disease (61).

Control of outbreaks

In a UK day care centre outbreak, rifampicin chemoprophylaxis administered to all child (irrespective of vaccination status) and staff contacts of 2 index cases resulted in complete eradication of Hib pharyngeal carriage among contacts when re-tested a month later and no further cases of Hib disease (84). In addition to household and day care settings, outbreaks of Hib disease have been reported in close communities (85) as well as paediatric (12) and geriatric hospital settings (86). Rifampicin chemoprophylaxis has been used with the aim of interrupting transmission in these circumstances. However, the numbers involved in these outbreaks have been small and, in most instances, chemoprophylaxis constituted only one of a number of control measures undertaken.

Use of vaccination following a case of Hib

For index cases, current UK guidelines recommend that unimmunised children younger than 10 years should be fully immunised after recovering from infection, while vaccinated children should have convalescent antibody levels measured and a booster dose of vaccine given if levels are below recommended protective levels (1). In circumstances where antibody levels cannot be tested, the child should receive an additional Hib-containing vaccine (1). The role of vaccinating household contacts to prevent secondary cases or control outbreaks is not known. Vaccination alone is probably ineffective in preventing outbreaks of Hib; the delay in antibody response to vaccination would not offer protection against most secondary cases, which occur within the first week after the index case. However, vaccination can be considered a valuable adjunct to chemoprophylaxis because it will boost immunity of previously vaccinated children with waning immunity and reduce Hib carriage, thereby preventing further transmission of the organism (41).

Guidelines

The following guidelines on prevention of secondary disease have been developed following a review of the epidemiology of invasive Hib disease, the impact of immunisation and the impact of various interventions. The Centers for Disease Control and Prevention (CDC) grading system was used for all recommendations as follows (87, 88):

• strongly recommended on the basis of more than 2 consistent, well-conceived, well-executed studies with control groups or longitudinal measurements
• recommended on the basis of more than one well-conceived, well-executed, controlled, or time-series study, or more than 3 studies with more limited execution
• indicated on the basis of previous scientific observation and theoretic rationale, but case-controlled or prospective studies do not exist
• not recommended on the basis of published literature recommending against a practice

Confirmed case of Hib

A confirmed case of Hib is defined as any individual who presents with clinical diagnosis of infection and Hib is isolated from a normally sterile site (Recommended). Hib conjunctivitis is not an indication for public health action, unlike meningococcal conjunctivitis (89).

Probable case of Hib (no longer included in 2024 guidance)

Following the dramatic fall in invasive Hib disease after the introduction of the Hib vaccine, most hospitals do not routinely perform H. influenzae typing. Instead, the isolates are usually sent to reference laboratories, resulting in a delay of up to a week before typing results become available. Using data from the 3 most recent calendar years (2020 to 2022), there were 1,391 invasive Hi cases, including 191 in children aged <5 years (Table 1). Of these, 1,222 (87.9%) were serotyped and only 20 (1.63%) were Hib, whereas other encapsulated types (a, c, d, e, f) and non-encapsulated Hi (ncHi) accounted for 231 (18.9%) and 991 (81.1%) of the cases, respectively. Hib was responsible for only 1.6% (20 out of 1,283) and 0% (0 out of 29) of blood and cerebrospinal fluid (CSF) culture isolates respectively. Overall, Hib was not a significant pathogen in any age group. Based on these data, there is no longer a need to define ’Probable Hib’. All invasive Hi isolates should be submitted for serotyping and public health action is only required for confirmed Hib cases.

Vulnerable individual (no longer included in 2024 guidance)

Give the very low risk of Hib disease in any age group, there is no longer a need to define a ’Vulnerable individual’ among close contacts of Hib (Recommended).

Household contact

As per previous guidance, the definition of a household contact is “any individual who has had prolonged close contact with the index case in a household type setting during the 7 days before the onset of illness” (Indicated).

Examples of a household contact include living or sleeping in the same house, boyfriends or girlfriends, and sharing a dormitory, flat or hospital ward with the index case. Other types of contact (for example, at work or school) would not be considered close contact, but each situation should be considered on its own merit, particularly if a vulnerable contact is involved and a close contact group can be clearly defined (Indicated).

Pre-school or primary school contact

The term ‘pre-school’ is used synonymously with playgroup, nursery, day care or crèche. Preschool and primary school contacts of an index case with invasive Hib disease should be defined separately for each case with the aim of identifying groups at higher risk of developing secondary Hib disease and, therefore, might benefit from prophylaxis (Indicated). Examples of pre-school or primary school contacts, therefore, may include staff and children in the same playgroup, class, school or social activity group as the index case.

Pre-school or primary school outbreak

A pre-school or primary school outbreak is considered to have occurred if 2 or more cases of invasive Hib disease have occurred among pre-school contacts (staff and children) within 120 days of each other (Indicated).

Chemoprophylaxis and vaccination

Timing of chemoprophylaxis

In order to maintain consistency of definitions with the UK meningococcal guidelines, chemoprophylaxis should be offered to the index case and all eligible contacts up to 4 weeks after onset of illness in the index case as soon as Hib is confirmed in the index case (Indicated).

Choice of antibiotic for chemoprophylaxis

Rifampicin at a dose of 20 milligrams per kilogram (mg/kg) (maximum 600mg) once a day for 4 days for adults and children older than 3 months is the prophylaxis of choice for eliminating carriage in the index case and among household contacts (Strongly recommended) because it is highly effective (eradication rate of 92 to 97%) and Hib resistance to rifampicin is extremely rare (<0.1%) in the UK.88 Infants younger than 3 months should receive 10 mg/kg once a day for 4 days (Strongly recommended). It should be noted that the dose and duration for rifampicin prophylaxis against Hib are different from those recommended for prevention of meningococcal disease (89).

Pregnant and breastfeeding women should also receive rifampicin prophylaxis if there is a vulnerable individual among the household contacts (Indicated) because the benefits of providing chemoprophylaxis to all household contacts, including pregnant and breastfeeding women, outweigh any potential risks.

Patients should be made aware of interactions with other medications such as anticoagulants, anticonvulsants and particularly oral contraceptives, and possible staining of secretions, including urine.

There is some evidence that third-generation intravenous cephalosporins may eliminate carriage in most cases, but published studies have been retrospective and uncontrolled, and involved a small number of cases only.

Once daily intravenous or intramuscular ceftriaxone (50 mg/kg in children younger than 12 years, one gram for older children and adults) once a day for 2 days is, therefore, recommended as an alternative agent in an individual who is unable to tolerate or develops an adverse reaction to rifampicin (Recommended). Side-effects are uncommon but include diarrhoea, hepatic dysfunction and blood disorders.

Treatment courses of oral ciprofloxacin (500mg in adults and children older than 12 years, 250mg for children aged 5 to 12 years, 125mg for children 2 to 4 years) twice a day for 5 days or azithromycin (10 mg/kg, maximum dose 500mg) once a day for 3 days may be used as alternatives, but their effectiveness in eradicating Hib colonisation among healthy individuals has not been determined (Indicated). The use of ciprofloxacin in paediatrics was previously limited because of concerns regarding irreversible quinolone-induced arthropathy documented in juvenile animal models, although such effects have not been observed despite extensive use (91 to 93). Ciprofloxacin suspension is licensed for other indications in children over one year of age (94) and has been recommended for prophylaxis against meningococcal disease in adults and children (89).

Hib vaccination

The current UK infant immunisation programme recommends a dose of Hib-containing vaccine at 8, 12 and 16 weeks age, followed by a booster dose at one year of age (Strongly recommended). The choice of Hib-containing vaccine to be used at different ages will depend on what other immunisations the child has already received and on the availability of suitable preparations. Three Hib-containing vaccines are currently available in the UK: Infanrix Hexa® 6-in-1 vaccine or Vaxelis® 6-in-1 vaccine (diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B and Hib) which are recommended for infant immunisation), and Mentorix® (Hib/meningococcal C combination vaccine) which is the recommended booster at one year of age.

Unimmunised and partially immunised children of those with unknown or uncertain immunisation history should be immunised according to the UKHSA guidance Vaccination of individuals with uncertain or incomplete immunisation status (Recommended).

Recommendations

The 2024 guidance now recommends public health action for all confirmed cases of Hib. This guidance supersedes previous recommendations for public health action only if there is a child under 10 years of age or a vulnerable individual in the household.

Index case

Given the very low incidence of invasive Hib disease, all index cases with confirmed invasive Hib disease (any age) should now receive rifampicin chemoprophylaxis prior to hospital discharge (Indicated).

Unimmunised and partially immunised index cases younger than 10 years should complete the recommended immunisations according to UKHSA guidance (see Hib immunisation above) (Strongly recommended).

Measuring anti-Hib antibodies and re-vaccinating children with invasive Hib disease after acute infection is not recommended (Recommended). Measuring of anti-Hib antibodies around 4 weeks after acute infection (and offering an additional dose if antibodies are below 1 mg/mL) may be considered by a clinician as part of an immunological work-up (including total immunoglobulin levels and subclasses) in a child with a history of recurrent infections and/or suspected underlying immune problem (Recommended).

Household contacts

Given the very low incidence of invasive Hib disease nationally, household contacts of a confirmed case will now be the main group with the highest risk of secondary Hib disease. Therefore, the index cases and all household contacts of the index case with confirmed invasive Hib disease should receive chemoprophylaxis (Recommended). This guidance is now in line with current recommendations for public health management of household contacts of a case with invasive meningococcal disease.

Chemoprophylaxis should be given to household contacts as soon as the diagnosis of Hib is confirmed in the index case (Recommended).

If there is a delay in typing of an invasive H. influenzae isolate, chemoprophylaxis should still be offered immediately to household contacts as soon as Hib is confirmed – up to 4 weeks of the onset of infection in the index case (Indicated).

In addition, unimmunised and partially immunised children younger than 10 years in the household should complete their immunisations according to the UKHSA guidance (Strongly recommended).

Contacts in the pre-school or primary school setting

Following a single confirmed case of invasive Hib disease in a pre-school or primary school setting, the families of children attending the same preschool group or primary school as the index case should be informed to seek medical advice if their child develops a fever and/or becomes unwell (Indicated).

For settings where a group of children with high levels of contact approaching those in the household can be defined – for example, a small number of children attending the same child-minder for several hours each day – offering antibiotic prophylaxis to the close contact group should be considered, including staff (Indicated).

Families should also be encouraged to ensure that their children are up to date with all their routine immunisations (Strongly recommended).

In case of an outbreak (2 or more cases of Hib disease within 120 days), as well as the above, chemoprophylaxis should also be offered to all room contacts, including staff (Recommended).

In addition, unimmunised and partially immunised children younger than 10 years should complete should complete their immunisations according to the UKHSA guidance (see Hib immunisation above) (Recommended).

Conclusions

The introduction of the Hib conjugate vaccine into national infant immunisation programmes has dramatically reduced the incidence of invasive Hib disease across all age groups. The new prevention guidelines take into account the most recent UK Hib epidemiology. Hib is currently very rare, especially in young children. Where indicated, a short course of rifampicin chemoprophylaxis remains highly effective in eliminating asymptomatic Hib carriage, thereby reducing the risk of re-infection, transmission and secondary disease.

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Tables

Table 1. Laboratory reports of invasive Haemophilus influenzae disease by age group and serotype in England and Wales during 2020 to 2022

	Under 1 month	1 to 11 months	1 to 4 years	5 to 14 years	15 to 44 years	45 to 64 years	65 to 74 years	75 to 84 years	85 and over	Unknown	Total
Total H. influenzae	41	72	78	40	187	281	253	216	222	1	1,391
Not serotyped (% total)	7 (17.1)	9 (12.5)	3 (3.8)	4 (10)	30 (16)	37 (13.2)	25 (9.9)	30 (13.9)	24 (10.8)	1 (100)	170 (12.2)
All serotyped (% total)	34 (82.9)	63 (87.5)	75 (96.2)	36 (90)	157 (84)	244 (86.8)	228 (90.1)	186 (86.1)	198 (89.2)	0 (0)	1,221 (87.8)
Hib (% known serotype)	0 (0)	1 (1.6)	1 (1.3)	0 (0)	5 (3.2)	8 (3.3)	2 (0.9)	1 (0.5)	2 (1)	-	20 (1.6)
H. influenzae a,c,d,e,f (% known )	0 (0)	15 (6.3)	20 (10.7)	10 (11.1)	15 (3.2)	54 (7.8)	43 (7.9)	32 (6.5)	22 (3)	-	211 (6.2)
ncHi (% known )	34 (100)	47 (74.6)	54 (72)	26 (72.2)	137 (87.3)	182 (74.6)	183 (80.3)	153 (82.3)	174 (87.9)	-	990 (81.1)
H. influenzae from blood	40	61	71	36	172	252	231	204	215	1	1,283
Not serotyped (% total)	6 (15)	1 (1.6)	2 (2.8)	2 (5.6)	23 (13.4)	19 (7.5)	10 (4.3)	20 (9.8)	21 (9.8)	1 (100)	105 (8.2)
All serotyped (% total)	34 (85)	60 (98.4)	69 (97.2)	34 (94.4)	149 (86.6)	233 (92.5)	221 (95.7)	184 (90.2)	194 (90.2)	0 (0)	1,178 (91.8)
Hib (% known serotype)	0 (0)	1 (1.7)	1 (1.4)	0 (0)	5 (3.4)	8 (3.4)	2 (0.9)	1 (0.5)	2 (1)	-	20 (1.7)
H. influenzae a,c,d,e,f (% known)	0 (0)	14 (6.7)	19 (11.6)	10 (11.8)	15 (3.4)	54 (8.2)	42 (8.1)	31 (6.5)	20 (3.1)	-	205 (6.5)
ncHi (% known)	34 (100)	45 (75)	49 (71)	24 (70.6)	129 (86.6)	171 (73.4)	177 (80.1)	152 (82.6)	172 (88.7)	-	953 (80.9)
H. influenzae from CSF	0	0	0	0	0	0	0	0	0	0	0
Not serotyped (% total)	1 (100)	7 (87.5)	1 (33.3)	-	4 (100)	7 (77.8)	0 (0)	2 (100)	-	-	22 (75.9)
All serotyped (% total)	0 (0)	1 (12.5)	2 (66.7)	-	0 (0)	2 (22.2)	2 (100)	0 (0)	-	-	7 (24.1)
Hib (% known serotype)	-	0 (0)	0 (0)	-	-	0 (0)	0 (0)	-	-	-	0 (0)
H. influenzae a,c,d,e,f (% known )	-	1 (0)	1 (0)	-	-	0 (0)	0 (0)	-	-	-	2 (0)
ncHi (% known )	-	0 (0)	1 (50)	-	-	2 (100)	2 (100)	-	-	-	5 (71.4)

Table 2. Hib carriage among unvaccinated children before the introduction of routine Hib vaccination

Country	Year	Age (years)	Population surveyed	Number of children	Hib carriage rates %	Reference
Alaskan Eskimos	1981	≤5	Population-based	121	5.0	96
China	2000	<5	Children with diarrhoea or dermatitis	214	1.9	97
Denmark	1990	≤8	Day care centres	265	0.0	98
Dominican Republic	1998	<4	Population-based	983	7.7	27
England	1995	3 to 4	Population-based	79	6.3	43
England and Wales	1992	1 to 4	Local playgroups, nurseries and child welfare clinics	1,531	4.0	46
Finland	1991	3	Child health centre	398	3.5	42
Gambia	1992	1 to 2	Population-based	1,994	11.0	45
Hong-Kong Chinese	1995	≤5	Population-based	621	0.0	99
Hong-Kong Vietnamese	1995	≤5	Population-based	300	1.3	99
Indonesia	1998	≤2	Population-based	484	4.6	26
Japan	1997	<4, 9, 13	Population-based	474 154 167	0.8 3.2 3.0	28
Papua New Guinea	1993	<3	Population-based	100	9.0	100
Swedish	1990	≤6	Random day care centre	49	8	32
Thailand	2005	<5	Hospital outpatients	492	7.0	29
Turkey	2000	<10	Child health clinics, day care centres and elementary schools	1,382	7	101
Turkey	2002	7 to 12	School students	300	3	102
United States	1985	≤8	Day care centre	66	10	33
United States	1979	25 months*	4 day care centres	98	1.0	67
United States	1979	18 months*	Child health centres, not attending day care	58	6.9	67
Wales	1986	≤6	Routine health checks or primary schools	996	1.1

*Median age.

Table 3 shows secondary attack rate among US household contacts within 30 days of hospitalisation of the index case. It was possible to combine studies on secondary attack rates in households because the chi-squared test for heterogeneity showed that the attack rates were not significantly different (p=0.4 for any Hib disease, p=1.0 for both the <2 year old and <4/<5 year old age groups; for Hib meningitis, p=0.6 for < 2 year old, p=0.9 for the <4/<5 year old and p=0.10 for the ≥4 year old age group).

Table 3. Secondary attack rate among US household contacts within 30 days of hospitalisation of the index case

Age of secondary case	Any invasive Hib attack rate % (95% CI)* [numbers]	References	Hib meningitis attack rate % (95% CI)* [numbers]	References
<2 years	1.8 (0.04 to 9.4) [1/57]	53, 56	3.8 (1.4 to 8.0) [6/159]	55, 57
<4 or ≤5 years	2.0 (0.5 to 5.0) [4/202]	53,56	2.1 (1.1 to 3.5) [14/676]	54, 55, 57
≥4 years	0 (0 to 0.8) [0/479]	53	0.02 (0.001 to 0.13) [1/4,256]	54, 55

*Binomial exact confidence intervals (CI).

Table 4 shows secondary attack rate among US day care contacts within 60 days of hospitalisation of the index case of any invasive Hib disease. Studies on secondary attack rates in day care centres were found to be heterogeneous for each age group (p=0.011 for the <2 year old age group and p=0.003 for the <4/<5 year old age group) and, therefore, are presented separately.

Table 4. Secondary attack rate among US day care contacts within 60 days of hospitalisation of the index case of any invasive Hib disease

Age of secondary case		Attack rate % [numbers]
<2 years	3.2 [1/31]	0 [0/361]	0 [0/361]	2.7 [10/376]	1.7 [5/292]
<4 or ≤5 years	1.1 [1/91]	0.2 [1/487]	0 [0/960]	1.2 [6/486]	0.4 [8/2024]
≥4 years	0 [0/70]	0 [0/87]	-	-	0 [0/237]
Reference	53*	59	60	51	78

*30 days follow-up.

Table 5 shows the effectiveness of rifampicin in preventing secondary Hib disease in household contacts 30 days after hospitalisation of the index case (40). The protective efficacy of rifampicin was calculated using the formula: 1- (risk with rifampicin / risk with no rifampicin).

Table 5. Effectiveness of rifampicin in preventing secondary Hib disease in household contacts 30 days after hospitalisation of the index case

Age of secondary case	No rifampicin attack rate % [numbers]	Rifampicin attack rate % [numbers]	Protective efficacy of rifampicin (95% CI)*
<2 years	0 [0/33]	0 [0/26]	-
2 to 3 years	3.3 [3/92]	0 [0/69]	100 (−199 to 100)%
<4 years	2.4 [3/125]	0 [0/95]	100 (−194 to 100)% (p=0.26)
≥6 years	0 [0/406]	0 [0/242]	-

*Binomial exact confidence intervals (CI).

Table 6 shows the effectiveness of rifampicin in preventing secondary Hib disease in day care contacts 30 to 60 days after hospitalisation of the index case. The protective efficacy of rifampicin was calculated using the formula: 1- (risk with rifampicin / risk with no rifampicin).

Table 6. Effectiveness of rifampicin in preventing secondary Hib disease in day care contacts 30 to 60 days after hospitalisation of the index case

Age of secondary case	No rifampicin attack rate % [numbers]	rifampicin attack rate % [numbers]	Protective efficacy of rifampicin (95% CI)*	p-value	References
<2 years	1.51 [16/1,060]	0.13 [1/799]	92 (37 to 99)%	p=0.002	53, 59, 61, 78
2 to 3 years	0.42 [2/480]	0 [0/460]	100 (−320 to 100)%	p=0.5	53, 59, 78
≥4 years	0 [0/324]	0 [0/500]	-		59, 78
≥6 years	0 [0/40]	0 [0/93]	-		53
Total	1.14 [18/1,580]	0.07 [1/1,352]	94 (52 to 99)%	p=0.003

*Binomial exact confidence intervals (CI).

Authors and contact

Prepared by Fariyo Abdullahi and Shamez Ladhani.

For queries relating to this document, please contact:

Dr Shamez Ladhani
Immunisations and Vaccine Preventable Diseases Division
UK Health Security Agency
61 Colindale Avenue
London NW9 5EQ

Email: [email protected]