Tuberculosis
With nine million new cases in 2004, resulting in 1.7 million deaths, tuberculosis is a leading infectious cause of morbidity and mortality worldwide (15). The resurgence of tuberculosis in many countries is attributable to its interaction with HIV infection, which has pernicious effects.
Tuberculosis is the leading cause of death among people with HIV, while infection with HIV is the most potent risk factor for a latent tuberculosis infection to convert to active disease (16). Although tuberculosis most commonly affects the lungs (the usual site of primary infection), it can cause disease in any part of the body as a consequence of haematogenous spread from the lung. The proportion of all cases of tuberculosis that are extrapulmonary (i.e. in sites other than the lungs) varies between countries but is typically about 10–20%. Among extrapulmonary cases, the most common sites involved are the lymph nodes and the pleura, but the sites of tuberculosis associ- ated with neurological disorders (meninges, brain and vertebrae) also constitute an important group. Meningeal tuberculosis has a high case-fatality rate, and neurological sequelae are com- mon among survivors. Cerebral tuberculoma usually presents as a space-occupying lesion with focal signs depending on the location in the brain. Vertebral tuberculosis usually presents with local pain, swelling and deformity, and there is risk of neurological impairment because of spinal cord or cauda equina compression.
The diagnosis of nervous system tuberculosis is often diffi cult, because of its nature of great simulator and also because of limited access to methods to confi rm it (17). Diagnosis depends on epidemiological and clinical data and fi ndings during cerebrospinal fl uid (CSF), neuroimaging and
bacteriological studies. Although not a direct consequence of tuberculosis, peripheral neuropathy can occur in tuberculosis patients as a side-effect of treatment with isoniazid, especially among patients who are malnourished, abuse alcohol, or are infected with HIV.
There are important public health approaches to the primary prevention of these tuberculosis- related conditions and to the secondary prevention of their adverse consequences. The most important overall approach to primary prevention consists of cutting the chain of transmission by case-fi nding and treatment. This approach is the basis of the international tuberculosis control strategy known as DOTS, which forms a central pillar of WHO’s new strategy for its Stop TB campaign (16). Although BCG vaccination has little impact in reducing the number of adults with infectious pulmonary tuberculosis, it is of crucial importance in preventing disseminated and severe cases of disease (including tuberculosis meningitis) in children. Therefore, in countries with high tuberculosis prevalence, WHO recommends a policy of routine BCG immunization for all neonates as part of the Expanded Programme on Immunization (EPI). It is estimated that the 100 million BCG vaccinations given to infants worldwide in 2002 will have prevented 30 000 cases of tuberculosis meningitis in children during their fi rst fi ve years of life (18). The primary prevention of isoniazid-induced peripheral neuropathy is by routine administration of pyridoxine to tuberculosis patients.
The main public health approach to the secondary prevention of the adverse consequences of tuberculosis disease of the meninges, brain and vertebrae is through promoting the application of the International Standards for Tuberculosis Care (19) to ensure prompt diagnosis and effective treatment. High-quality tuberculosis care will result not only in patients having the best possible outcome of treatment, but also in the public health benefi t of decreased tuberculosis transmission by infectious cases and thereby, ultimately, an impact on the global burden of all tuberculosis cases, in- cluding those associated with neurological disorder. The key steps in diminishing the global burden of neurological disorder associated with tuberculosis are to promote: investment in full implementation of the Stop TB strategy and International Standards for Tuberculosis Care; full immunization cover- age so that all neonates are protected by BCG from risk of disseminated and severe tuberculosis;
and better understanding of the epidemiology of tuberculosis disease associated with neurological disorder through improved surveillance in countries with high tuberculosis prevalence.
Leprosy neuropathy
Leprosy is the cause of the most common treatable neuropathy in the world, caused by Myco- bacterium leprae. The incubation period of the disease is about fi ve years: symptoms, however, can take as long as 20 years to appear. The infection could affect nerves by direct invasion or during immunological reactions. In rare instances, the diagnosis can be missed, because leprosy neuropathy may present without skin lesions (neuritic form of leprosy). Patients with this form of disease display only signs and symptoms of sensory impairment and muscle weakness, posing diffi culties for diagnosis, particularly in services where diagnostic facilities such as bacilloscopy, electroneuromyography and nerve biopsy are not available.
Delay in treatment is a major problem, because the disease usually progresses and the resulting disability if untreated may be severe, even though mycobacteria may be eliminated. Delay in treat- ment is, however, usually a result of delayed presentation because of the associated stigma. People with long-term leprosy may lose the use of their hands or feet because of repeated injury resulting from lack of sensation. Early diagnosis and treatment with the WHO-recommended multidrug therapy (MDT) is essential in order to prevent the disease from progressing and resulting in disability.
Bacterial meningitis
Bacterial meningitis is a very common cause of morbidity, mortality and neurological compli- cations in both children and adults, especially in children. It has an annual incidence of 4–6
cases per 100 000 adults (defi ned as patients older than 16 years of age), and Streptococcus pneumoniae and Neisseria meningitidis are responsible for 80% of all cases (20). In developing countries, overall case-fatality rates of 33–44% have been reported, rising to over 60% in adult groups (21). Bacterial meningitis can occur in epidemics that can have a serious impact on large populations.
The highest burden of meningococcal disease occurs in sub-Saharan Africa, which is known as the “meningitis belt”, an area that stretches from Senegal in the west to Ethiopia in the east, with an estimated total population of 300 million people. The hyperendemicity in this area is at- tributable to the particular climate (dry season between December and June, with dust winds) and social habits: overcrowded housing at family level and large population displacements for pilgrim- ages and traditional markets at regional level. Because of herd immunity (whereby transmission is blocked when a critical percentage of the population had been immunized, thus extending protection to the unvaccinated), the epidemics occur in a cyclical fashion.
Meningitis is characterized by acute onset of fever and headache, together with neck stiffness, altered consciousness and seizures. The diagnosis can be confi rmed by its clinical characteristics and bacteriological and immunological analyses of the CSF. Antibiotic treatment is effective in most cases but several neurological complications can remain, such as cognitive diffi culties, mo- tor disabilities, hypoacusia and epilepsy. In a recent review, treatment with corticosteroids was associated with a signifi cant reduction in neurological sequelae and mortality (22).
Progress is more likely to come from investigations into preventive measures, especially the use of available vaccines and the development of new vaccines. Meningitis caused by Haemophilus infl uenzae type B has been nearly eliminated in developed countries since routine vaccination with the H. infl uenzae type B conjugate vaccine was initiated. The introduction of conjugate vaccines against S. pneumoniae may substantially reduce the burden of childhood pneumococcal menin- gitis and may even produce herd immunity among adults. The approval in 2005 of a conjugate meningococcal vaccine against serogroups A, C, Y and W135 is also an important advance that may decrease the incidence of this devastating infection. Local and nationwide surveillance, in- cluding the laboratory investigation of suspected cases, is critical for early detection of epidemics and the formulation of appropriate responses.
Tetanus
Tetanus is acquired through exposure to the spores of the bacterium Clostridium tetani which are universally present in the soil. The disease is caused by the action of a potent neurotoxin produced during the growth of the bacteria in dead tissues, e.g. dirty wounds or — for neonatal tetanus — in the umbilicus following non-sterile delivery. Tetanus is not transmitted from person to person:
infection usually occurs when dirt enters a wound or cut. At the end of the 1980s, neonatal tetanus was considered a major public health problem. WHO estimated that, in 1988, 787 000 newborn children died of neonatal tetanus, a rate of 6.5 cases per 1000 live births. In 2004 the number of reported cases was 13 448. A worldwide total of 213 000 deaths were estimated to have occurred in 2002, 198 000 of them concerning children younger than fi ve years of age (23).
Unlike poliomyelitis and smallpox, the disease cannot be eradicated because tetanus spores are present in the environment. Once infection occurs, mortality rates are extremely high, especially in areas where appropriate medical care is not available. However, this death toll can be prevented.
Neonatal tetanus can be prevented by immunizing pregnant women and improving the hygienic conditions of delivery. Adult tetanus can be prevented by immunizing people at risk, such as work- ers manipulating soil; others at risk of cuts should be also included in the prevention measures.
Some forms of toxoid are available (DTP, DT, TT or Td) and at least three primary doses should be given by the intramuscular route. Vaccination coverage with three doses of DTP is more than 80%
for most countries around the world. The Maternal and Neonatal Tetanus elimination initiative was
launched by UNICEF, WHO and the United Nations Population Fund (UNFPA) in 1999, revitalizing the goal of elimination of maternal and neonatal tetanus as a public health problem, defi ned as less than one case of neonatal tetanus per 1000 live births in every district of every country.