Community acquired bacterial meningitis in Cuba: a follow up of a decade

Despite the advances in antibiotic therapy and vaccines as well as the availability of sophisticated intensive care reached in the past century and the ongoing, community acquired Bacterial Meningitis (BM) remains a serious threat to global health [1, 2].

Several issues support its relevance. BM is a leading cause of high morbidity in all ages but young children are at great risk, especially infants. This often fatal disease accounts for an estimated annual 170 000 deaths worldwide and case fatality rates (CFR) remain at 5-10% in industrialized countries, and are even higher in the developing world [1, 3–6]. Between 10-20% of survivors develop permanent sequel such as epilepsy, mental retardation or deafness and other neurological disabilities which may contribute to the Global Burden of BM measured as the disability adjusted life years (DALYs) [7].

A great variety of bacteria can cause BM although three species, Streptococcus pneumoniae), Neisseria meningitidis and Haemophilus influenzae type b (Hib) are responsible for most cases of bacterial meningitis occurring beyond the neonatal period, causing more than 80% of cases worldwide [1]. On the other hand a decrease of the susceptibility to conventional and new antibiotics may difficult the treatment [3]. Fortunately there are vaccines against the most common aetiological agents, with high efficacy [1–3], but their use and coverage are unequal depending on public health and economical resources in each country.

Surveillance remains an essential tool to identify the cases, the aetiological agents, and other important epidemiological variables. Routine surveillance systems differ according to the different regions. In the developed world they are mostly based on mandatory notifications of infectious diseases and more recently on laboratory [8–11], while in developing countries are based on case reports and epidemics notifications [12], as well as on hospital sentinel surveillance [13].

First cases of cerebrospinal meningitis in Cuba were reported in 1916. Since 1961 a Mandatory Report of Diseases, including BM, was implemented by Public Health Ministry. Later in 1979 and during an invasive meningococcal disease epidemic, due to serotypes B and C, a special nationwide surveillance known as Direct Information System arose with the interest to achieve a completeness and timeliness in reporting cases [14, 15]. In 1983 it was added an automated questionnaire for reporting. Afterwards, in 1998, all causative bacteria were put under surveillance through an updated questionnaire including complementary information about confirmed cases and different of those routinely collected, remaining as the national data source for the National Program for Control and Prevention of the Neurological Infectious Syndrome (NPCPNIS) [16].

The aim of this paper was to characterize the main epidemiological features of BM in Cuba during a ten year period, as well as to assess the association with mortality of some variables reported by surveillance.

Likewise those of developed countries [9–11], BMSS has been useful and proficient providing and synthesizing critical and multidisciplinary information [16, 17] for more than a decade, fulfilling all suitable surveillance system attributes [17, 18]. Changes implemented in 1998 allowed collecting data which contributed to assess main objectives of both, the National Immunisation Program (NIP) and the NPCPNIS.

However, very few cases of BM might have been missed or misdiagnosed despite the strict control of surveillance and reporting. On the other hand, possible information bias from patients and their relatives was reduced after successive interviews by epidemiologists at hospital and home, as a part of the hot bed control.

Infants and elderly are the most affected age groups by BM and the overall incidence in the study was low and comparable with those of the developed world.

Declining of BM incidence may be the result of the rational use of preventive and control measures nationwide. The impact of vaccination against N. meningitidis serotype B and C carried out in 1989 (vaccination campaign targeted to population under 20 years with nearly 95% coverage) and continued in 1991 by the NIP (VA-MENGOC BC^®, two dose schedule at 3 and 5 months of age), as well as the successful vaccination against Hib carried out in 1999 in children (three dose schedule at 2, 4, 6 months and a booster dose at 18 months) has been reported [19, 20]. Therefore, continuous vaccination and high coverage (>95%) achieved in population under 11 years old (Hib) and under 40 years old (N. meningitidis) along this period, may explain not only the decreasing trend of the incidence in targeted population, but the decrease in other age groups (herd immunity) [19, 20]. At present, S. pneumoniae remains the only major causative bacteria of BM in Cuba without specific vaccination control; however the incidence was low and comparable with those achieved by countries that undertook pneumococcal vaccination [21].

Public Health System implemented in Cuba since 1959, is based on nationwide free health service with total access for every citizen to high quality medical assistance, hospitalization, vaccination, social assistance and other health services [19], and undoubtedly also has contributed to BM decreasing trends.

Infants were the most affected group by BM as also occurred in other countries [22, 23]. In our study BM was more frequent in this group between two and six months of age, period in which they may have lost the mother protective antibodies and still are not completely protected by vaccines. Other authors report the highest rates of BM among infants between six and twelve months [23, 24].

In our series overall and annually male incidence showed a significant predominance over female, coincidently with other author's findings [25, 26]. Some sex-specific differences in physical interaction with others and risk behaviour, may explain these findings and will likely require a deeper exploration.

There are a number of stages in the interaction between a sick person and the health care system, at which management decisions may critically affect the speed with which medical treatment is initiated. Delays in receiving appropriate medical care to BM patients more frequently occurs when at home, the signs of disease are not recognised. Once it has been recognised that severity of disease requires medical attention, difficulties may be experienced in consulting with the doctor (not available, low medical attention coverage, lack of transportation, remoteness and others). Once the doctor has seen the patient, the signs of serious illness might not be recognised (lack of familiarity with the condition, inexperience) [27–29] and therefore a delay in hospitalization and specific treatment may occur.

Fatal outcome depends on many factors but care-seeking behaviour in the population, referral practices to hospitals, timely and adequate medical care and specific treatment, the underlying conditions on the patient and the virulence of the strains are the most important [30–34].

NPCPNIS in Cuba recommend the prompt initiation of antibiotic therapy in intensive care unit conditions for all confirmed cases of BM [16]. Regardless of known relationship between increase of mortality and delay in medical attention and hospitalization, that association was not found in our study, showing that timely medical advice and care was received by the majority of patients.

In our study, CFR in infants (17.0%) was coincident to those reported by authors [22, 35–37], but high numbers observed, especially among adults [38, 39] and older adults [40, 41], was probable due to other factors including poor and untimely recognition of symptoms in the elderly.

It was observed association of the fatal outcome with some societal groups (housewife, pensioned, imprisoned, unemployed), as well as the infection caused by S. peumoniae and other identified bacteria. These societal groups might be often more vulnerable due to socioeconomic factors and underlying conditions. Also, poor living conditions at home and gathering places as well as the infection by high virulence strains as Streptococcus and Staphylococcus ssp.might contribute to increase this association. It is important to remark that recently have been reported cases of adrenal haemorrhage as a result of streptococcal infection, evidencing the virulence of this agent [42]. Furthers studies must be undertaken to evaluate more precisely this factors and interactions.

Is interesting how the highest incidence of BM in Cuba is mainly clustered in the central provinces. The Cuban island is long and narrow, and the central region has higher solar radiation and more climate variability than other regions. The combined physical-geographic characteristics and socioeconomic conditions may explain this high incidence [43] and should be more precisely assessed in future studies.

Two well-defined seasons are recognised in Cuba: the rainy or summer (May to October) and the dry or winter (November to April). Since 1990s, climate conditions in winter seasons were projected to be warmer and rainier, and rainy season were projected to be drier and hotter, then this climate conditions are associated with increase of respiratory communicable diseases [43].

Main causative pathogens of BM have each one a peculiar seasonal pattern according to regions of the world. In a study in Lazio, Italy [22], main peaks were observed in January and March, coincident with our results. Seasonal increases of BM observed in our study might be related with seasonal distribution of the main causative pathogens.

A decade of BM surveillance in Cuba evidenced a reduction in the incidence after using effective preventive and control measures (health education, high coverage vaccination against meningococcus B and C, and Hib, timely hotbed control and others), but still vital efforts are required to decrease CFR, especially in the elderly and other societal groups included in the study.

Future vaccination against S. pneumoniae in high risk population will decrease even more the incidence of these lethal infections.

Continuous monitoring of BM and further studies will make possible to assess the need for putting new strategies for the control of these severe groups of diseases in the benefit of the population.