Meningococcal disease (MD) is caused by the bacterium Neisseria meningitidis, also called meningococcus. It is an encapsulated, gram-negative diplococcus, and a facultative anaerobe with fastidious growth requirements. There are at least 13 serogroups of meningococci, with the most important being serogroups A, B, C, Y and W135.
About 5-10% of the population are asymptomatic carriers of Neisseria meningitidis bacteria, which are spread via respiratory and throat secretions such as saliva / spit of an infected person. Someone within a meter of an infected person can be infected when they sneeze or cough. Household contacts, roommates, or anyone with direct contact with a patient's oral secretions (such as a boyfriend or girlfriend) should be considered at increased risk of getting the infection. The bacteria are not spread by casual contact or by simply breathing the air where a person with meningococcal disease has been. Meningococcal disease is not highly communicable, with only up to 4% of households of patients experiencing secondary cases.
Anyone can get meningococcal disease, but certain groups of people are at increased risk. Travelers who spend a lot of time with local populations in the meningitis belt during a large outbreak have the highest risk of contracting the disease. In addition to the meningitis belt, travelers to the Hajj pilgrimage in Saudi Arabia, and those living in army barracks are also at risk, due to very close proximity to others in crowded conditions. Young children have the highest risk for meningococcal disease, but 60% of cases occur in adolescents and adults. Children younger than 6 months are protected by maternal antibodies, although occult meningococcemia, an uncommon form of infection, affects children aged 3-24 months. A less dramatic peak in incidence occurs among teenagers and college students; this may be due to increases in close interpersonal contact in these populations, as seen in first year residents of university hostels. Asplenic patients and people with complement deficiency are also at risk.
The incubation period is usually 3-4 days, but ranges from 2-10 days. Meningococcal disease presentation may be non-specific in the early stages and a high index of suspicion should be maintained. Disease presentation may also be acute and rapidly progressive. Only 50% of patients present with meningococcaemia, and a rash is usually but not always present.
Of cases of invasive meningococcal disease, 30-50% present with meningitis alone, 40% have meningitis with septicemia, and 7-10% have septicaemic features. Meningococcal meningitis is the most common (50%) form of invasive MD. The classical symptoms of fever, headache and neck stiffness may be absent or slow to develop, particularly in young infants. Nausea, vomiting and photophobia (light sensitivity) are common symptoms. Most (75%) meningococcal meningitis patients also have meningococcal sepsis (meningococcaemia). Meningococcal septicaemia (meningococcaemia) occurs without meningitis in 5-20% of invasive MD cases. Classical symptoms include abrupt onset of fever accompanied by a petechial or purpuric rash from bleeding into the skin. Often bleeding into the adrenal glands leads to hypotension, shock and multi-organ failure, known as Waterhouse-Friedrichsen syndrome.
A rare chronic form of meningococcal septicaemia presents with intermittent fevers, rash, arthralgia and headaches. Meningococcal pneumonia occurs in 5 - 15% of cases. Other less common presentations include meningococcal arthritis, which occurs in 2%, meningococcal otitis media which occurs in 1%, and meningococcal epiglottitis which occurs in less than 1% of cases. Other focal infections include conjunctivitis, purulent pericarditis, endocarditis and myocarditis, which tend to occur in association with meningococcal septicaemia.
The case-fatality rate of meningococcal infections varies depending on the prevalence of disease, the clinical form of disease, and socioeconomic conditions. In the United States, the overall case-fatality rate is approximately 10%, and can be as high as 15% in developed countries despite antibiotic treatment. GERMS-SA reported that in 2015, the case-fatality rate was 14% in patients with meningococcal bacteraemia, and 15% in patients with meningococcal meningitis.
Complications of meningococcemia may occur at the time of acute disease or during the recovery phase. Patients with fulminant meningococcemia may develop respiratory insufficiency and need mechanical ventilation. Severe infection may progress to vascular insufficiency resulting in shock. Patients with profound shock can develop adrenal infarction (Waterhouse-Friedrichsen syndrome). Severe sepsis also results in thrombosis and necrosis in large areas of skin with resultant infarction and gangrene of limbs and digits. Septic arthritis and purulent pericarditis can occur but are rare. Meningococcemia has the highest case-fatality rate of about 40%, despite appropriate antibiotic treatment, but can be as high as 70% in developing countries. A higher mortality rate of 40-80% in patients with meningococcemia is associated with the acute onset of petechiae less than 12 hours before admission. Meningococcemia associated with disseminated intravascular coagulation has a mortality rate of higher than 90%.
Isolated meningococcal meningitis has a better prognosis, with a 5% mortality rate. Meningococcal meningitis may progress to mental stupor, or coma, which may be related to increased intracranial pressure. Other rare complications of meningitis include acute and delayed venous thrombosis, which usually manifests as a focal neurologic deficit. As many as 20% of MD survivors have permanent sequelae, such as hearing loss, neurologic damage, or loss of a limb.
Globally, 5%–10% of the population may be carriers of N. meningitidis. However, invasive disease is rare in non-epidemic areas. The highest burden of meningococcal disease occurs in the African Meningitis Belt, an area stretching from Senegal in the west to Ethiopia in the east. Serogroup A is predominant in developing countries, being predominant in the African Meningitis Belt, followed by serogroups C and W135. Serogroup B predominates in Europe, North America and New Zealand. Serogroup C is found in both developed and developing countries, and has caused large outbreaks in Africa, Asia and South America.
From 2000 to 2005 a total of 2 135 MD cases were reported from South Africa, with most occurring in Gauteng Province (52%) and the Western Cape (23%). Serogroup B has predominated in the Western Cape for several decades, while serogroup A was predominant in Gauteng Province, but by 2005 serogroup W135 became the predominant serogroup. The GERMS-SA surveillance system found 192 and 156 cases in 2014 and 2015 respectively. Most cases occurred in the Western Cape and Gauteng, although the Eastern Cape had the second highest incidence rate, in both years. Serogroup B was predominant in 2015, followed by serogroup W.
TB is caused by a highly contagious group of bacteria called the Mycobacterium tuberculosis complex, of which Mycobacterium tuberculosis (MTB) is the major cause of disease. MTB is taken up by macrophages within the host’s lungs, but instead of being killed by these cells as is the case with other bacteria, MTB evades being killed. Macrophages containing MTB collect together to form granuloma. MTB can remain dormant in these granuloma for weeks, months, years, decades or even a whole lifetime, and this is called latent TB infection.
People with latent TB infections are not infectious and thus cannot transmit TB. Only those with TB disease are highly infectious, and can spread TB to others. TB is spread by expelling TB-carrying droplets into the air by sneezing, coughing, spitting, or even just by singing or speaking. Risk factors for transmission are mainly poverty-related, and include overcrowded living conditions with poor ventilation, and poor nutrition.
In developing countries, a large proportion of the population may be infected, although most will not develop TB disease (i.e. they will have latent infection). Those at high risk of infection include close contacts of people with TB disease, especially poor people living in crowded informal settlements. Healthcare workers who work with TB patients or their specimens are also at high risk of being infected. Infants, children and adolescents are also at high risk of being infected. Only a small proportion of those who are infected are at risk of developing TB disease. People with untreated HIV infections or other immunodeficiency conditions (eg: cancer patients, especially those undergoing chemotherapy; transplant patients on corticosteroids); diabetics; and substance abusers are some of the groups at high risk of developing TB disease. Because children under the age of 4 years have immature immune systems, they are also a high risk group. Infants are especially vulnerable to developing fatal disseminated TB diseases such as milliary and meningeal TB.
People with latent TB infection have no symptoms. When the immune system cannot control a latent infection, it becomes active and symptoms of TB disease appear. Pulmonary TB is the most common type of TB disease. Symptoms of pulmonary TB include coughing for at least three weeks, with the cough sometimes producing phlegm that is sometimes blood stained. Other symptoms include pains in the chest; feeling tired or weak; losing weight for no reason; loss of appetite; chills; fever; and night sweats.
Most people who get infected with MTB do not develop TB disease, but have latent TB infections. However, these infections do become active in a small proportion of those who are infected, and these people develop TB disease. Also, a small proportion of people with latent TB infections reactivate these infections later in life, and develop TB disease. The probability of developing TB disease is much higher in HIV infected people. TB commonly affects the lungs and is then called pulmonary TB, but it can also affect all other tissues and organs including the bones and the brain, and it is then called extrapulmonary TB. Untreated TB disease commonly results in death. About 70% of HIV negative people with sputum smear-positive TB will die within 10 years without treatment; the death rate is higher and quicker in HIV positive people.
Effective drug treatments for TB disease have been around for more than 50 years, but widespread lack of adherence to drug regimens has led to the emergence of drug resistant TB, which in 2015 constituted 580 000 TB cases worldwide. Of these, 480 000 were multi-drug resistant (MDR-TB), while 100 000 were rifampicin resistant (RR-TB). Of the MDR-TB cases, 9.5% were extensively drug resistant (XDR-TB). The average cure rate for MDR-TB is 52%, while that for XDR-TB is only 28%.
Almost 1% of the global population are newly infected with MTB every year, while about a third have latent TB infection. Of these, a small proportion develop active TB disease, which in 2015 was estimated to have developed in 10.4 million people, 1 million of whom were children, while 1.8 million people died of TB in 2015. About 60% of incident cases in 2015 occurred in south-east Asia, Nigeria and South Africa. The case fatality rate in the WHO Afro region is about 20%. South Africa has one of the highest burdens of TB disease in the world, with an estimated 454 000 new cases in 2015. Although effective treatment for TB is widely available in the country, there were 25 000 and 73 000 TB deaths in HIV negative and positive South Africans respectively, in 2015.
complex, of which
is the major cause of disease
MTB is taken up by
macrophages within the host’s lungs, but instead of being killed by these cells as is the case with other
bacteria, MTB evades b
eing killed. Macrophages containing MTB collect together to form granuloma.
MTB can remain dormant in these granuloma for weeks, months, years, decades or even a whole lifetime,
and this is called latent TB infection.
Diphtheria is caused by an aerobic gram-positive bacillus called Corynebacterium diphtheriae. It is an acute, communicable disease. It affects mainly the pharynx and is characterised by a leathery pharyngeal membrane. The disease occurs worldwide. It was the major cause of childhood death before the introduction of the toxoid vaccine. The disease is toxin-mediated, thus only toxigenic strains of the organism can cause severe disease. C. diphtheriae can infect all mucous membranes, but the tonsils and pharynx are the most commonly infected. Humans are the only reservoir, and the organism is harboured in the nasopharynx of healthy asymptomatic people.Culture of the organism requires selective media containing telluride. If isolated, the organism must be distinguished in the laboratory from other Corynebacterium species that normally inhabit the nasopharynx and skin. Toxin production must also be confirmed in the laboratory.
The transmission route is via respiratory droplets spread from person-to-person. Transmission can also occur from contact with skin lesions or contaminated dressings and other fomites (articles contaminated by skin lesion discharges) as is seen in tropical areas. The basic case reproduction number (R0) (average number of successful transmissions in a totally susceptible population) for diphtheria is 6- 7, indicating a high level of infectivity. Patients remain infectious for the duration of active infection, which can last for four weeks without antibiotics. However, healthy chronic carriers remain infectious for months and should thus be identified and given a course of antibiotics to terminate shedding.
Unimmunised people living in countries where diphtheria is still endemic are at risk. Because the bacteria are carried by healthy asymptomatic people who remain untreated, outbreaks in countries with historically low vaccination coverage continue to occur. These days diphtheria is rare in developed countries. Before the introduction of the vaccine, infants and young children were most at risk. However, diphtheria outbreaks occur in developing countries among older children, adolescents and adults, while infants and young children are less frequently infected, especially in countries which now have wellfunctioning infant immunisation programmes.
The incubation period ranges from 1 to 10 days. The toxin causes local tissue destruction and pseudomembrane formation. When it enters the bloodstream it reaches all organs and tissues of the body, where it can cause myocarditis, neuritis, thrombocytopenia and proteinuria. The clinical manifestations depend on the site of infection. Pharyngeal and tonsillar diphtheria are the most common types of diphtheria, and are also the most severe since the toxin is easily absorbed from these sites. In addition to membrane formation, there is marked swelling of cervical lymph nodes forming a distinct collar reaching from ear to ear, filling out the whole space beneath the jaw creating a stridor (barking cough) and a bull’s neck appearance. Airway obstruction may occur suddenly due to aspiration of the dislodged pharyngeal membrane. Anterior nasal diphtheria is a milder form of the disease because there is little toxin absorbed at this site. It resembles the common cold, with a mucopurulent (mucous and pus) discharge. Sometimes blood is present in the discharge, and there is usually white pseudomembrane formation on the nasal septum.
The severity of the disease and complications are generally related to the extent of local disease. The most frequent complications of diphtheria are myocarditis and neuritis. Myocarditis may present as abnormal cardiac rhythms and can occur early in the course of the illness or weeks later, and can lead to heart failure. Myocarditis is often fatal. Neuritis most often affects motor nerves and usually resolves completely. Paralysis of the soft palate is most frequent during the third week of illness. Paralysis of eye muscles, limbs, and diaphragm can occur after the fifth week. Secondary pneumonia and respiratory failure may result from diaphragmatic paralysis. Other complications include otitis media and respiratory insufficiency due to airway obstruction, especially in infants. The overall case fatality rate for diphtheria is 5-10% with higher death rates among persons younger than 5 and older than 40 years of age. The photo on this slide is of a child who died from diphtheria on the 13th June 2016 in the Malappuram district of Karala in India, which has had a problem with anti-vaccination lobbying for a number of years.
Diphtheria occurred worldwide and was considered one of the leading causes of childhood death in the pre-vaccine era. Post vaccine introduction, the disease declined dramatically. In South Africa, prior to 2015 three laboratory confirmed cases had been reported in the past decade – one in 2008 (Western Cape), one in 2009 (Eastern Cape) and one in 2010 (Western Cape). On 15 March 2015, an outbreak was reported in KwaZulu Natal, which lasted until 12 June and involved 15 cases. Another two cases occurred in the same district of KZN in May 2016, and they were the same strain as the 15 cases identified in 2015. Only one of the cases from 2015 had been fully vaccinated against diphtheria. Of the 15 cases from 2015, 4 had died. In contrast, there have only been three deaths due to diphtheria in the UK since 1994.
Tetanus is caused by the spore-forming bacterium Clostridium tetani. C. tetani spores are found in soil, animal and human feces. The organism is sensitive to heat and cannot survive in the presence of oxygen, being an anaerobic micro-organism. The spores enter the body through breaks in the skin, and germinate anaerobically. Puncture wounds and wounds with a significant amount of tissue injury (eg necrotic tissues) are more likely to promote germination. The organism produces two exotoxins: tetanolysin and tetanospasmin. The function of tetanolysin is unknown. Tetanospasmin, which is absorbed into the bloodstream, causes the neurological symptoms of tetanus infection.
Several portals of entry have been documented, but in about 20% of cases, sources of infection may be unknown. C. tetani usually enters the body through a wound. Neonatal tetanus (NNT) results from unsterile treatment of the umbilical stump. Puncture wounds, circumcision, infected burns, postabortal sepsis, injection sites, guinea-worm sores, road traffic accident wounds, otitis media, surgical procedures performed with contaminated gloves or poorly sterilized catgut sutures, are some other portals that have been described. Tetanus in a non-communicable disease, meaning that it cannot be spread from person-to-person. Because it is present in the environment, it can never be eradicated.
Populations who are at high risk include those who have never been vaccinated, or who have not received their boosters. Neonates whose umbilical cords are cut with unsterile instruments, or whose umbilical stumps are covered with unsterile dressings, are at high risk of NNT. Mothers who have unsterile deliveries or abortions, are at high risk of maternal tetanus. Also heroin users, particularly those who inject themselves subcutaneously, are at high risk for tetanus. In addition, patients with puncture wounds, or contaminated, infected, or devitalized wounds, are considered tetanus-prone.
The incubation period ranges from 3 to 21 days. Three different forms of tetanus have been described based on the clinical findings. The 1st is local tetanus, which is uncommon. This involves rigidity of the muscles associated with the site of spore inoculation. Contractions may persist for many weeks before gradually subsiding. This form resolves spontaneously, and only 1% of cases are fatal. The 2nd form is cephalic tetanus, which is a rare form of the disease. This form occasionally occurs with otitis media (ear infections) or following injuries to the head. There is involvement of the cranial nerves, especially in the facial area. The 3rd form is generalised tetanus, which is the most common form, constituting 80% of reported cases. This form is characterized by painful muscular contractions, involving the jaw and neck muscles, resulting in “lockjaw”. Typical features of the tetanic spasms are the position of opisthotonus (i.e. backward arching of the head, neck and spine), and the facial expression known as “risus sardonicus” (a grin produced by a facial spasm). NNT is an example of generalized tetanus.
Laryngospasm and/or spasm of the muscles of respiration leads to interference with breathing. Fractures of the spine or long bones may result from sustained contractions and convulsions. Hyperactivity of the autonomic nervous system may lead to hypertension and/or an abnormal heart rhythm. Factors that affect mortality include the severity of spasms; duration of hospital stay; incubation period; onset time; immunisation status; socio-economic background and the type of initial care. The mortality rate of mild and moderate tetanus in developed countries is presently about 6%; for severe tetanus, it may reach as high as 60%, even in centres with high levels of expertise. Tetanus survivors often have serious psychological problems related to the disease and its treatment, which persist after recovery and may require psychotherapy. Previous vaccination status is directly related to severity of disease, with the case-fatality rate ranging from 6% for patients who had received one to two doses, to 15% for patients who were unvaccinated.
Immunisation programmes have decreased NNT deaths, and recent evidence suggests progress in the prevention of tetanus throughout the world. NNT is rare in developed countries, but is common in some developing countries and is associated with high mortality, with more than 257 000 annual deaths worldwide estimated in 2000-2003. NNT was eliminated (i.e. less than 1 case in 1000 live births in every district) in South Africa in 2002. Thanks to infant vaccination against tetanus, tetanus cases in children are rare in South Africa, with only one case of tetanus being reported in 2016. This case was an 11 year-old girl from Free State Province, who had previously not received any vaccinations.
Pertussis (whooping cough) is a bacterial respiratory infectious disease, caused by Bordetella pertussis. B. pertussis is a small, aerobic gram-negative bacillus which is specific to humans, gaining entry through and colonising the respiratory tract. B. pertussis produces multiple antigenic and biologically active components, including pertussis toxin, filamentous hemagglutinin, agglutinogens, adenylate cyclase, pertactin, and tracheal cytotoxin. These virulence factors help B. pertussis to attach to and invade host cells, leading to the clinical characteristics of pertussis. Following an infection by B. pertussis an individual develops immunity to the disease.
Pertussis is highly contagious and spreads very easily from person to person in droplets produced by an infected person while coughing and sneezing. The infection can also be passed on through direct contact with infected secretions from the mouth or nose. The basic case reproduction number (R0) (average number of successful transmissions in a totally susceptible population) for pertussis is 12-17, indicating an exceptionally high rate of infectivity. A person is most infectious in the early stages of their illness.
New-borns receive minimal antibody protection from their mothers, and it quickly wanes. Although pertussis infections commonly occur among children aged between 1-5 years, the disease is particularly severe and even fatal in infants. In adolescents and adults, pertussis is often unrecognized because its course is frequently asymptomatic. Adolescents and adults are significant sources of transmission of B. pertussis to unvaccinated infants. When pertussis occurs in infants, household contacts (primarily parents) are the source of infection in >75% of cases.
The incubation period of pertussis is commonly 7–10 days, with a range of 4–42 days. The clinical course of the illness is divided into three stages. The 1st stage is the catarrhal stage, which lasts 1-2 weeks, and is characterized by the subtle onset of coryza (runny nose), nasal congestion, red and watery eyes, sneezing, low-grade fever, and a mild, occasional cough, similar to the common cold. The 2 nd stage is the paroxysmal stage, which lasts 1-6 weeks. During this stage the cough becomes more severe, and this is when pertussis is usually diagnosed. This stage is characterised by bursts (paroxysms) of numerous, rapid coughs, apparently due to difficulty in expelling thick mucous from the airways. At the end of the paroxysm, a long inspiratory effort is usually accompanied by a characteristic high-pitched whoop. The convalescent stage, which is the 3rd stage, can take weeks to months, during which recovery is gradual. The cough gradually becomes less paroxysmal and thereafter disappears in 2 to 3 weeks.
The most common complication of pertussis in children is secondary bacterial pneumonia, which is the most common cause of death due to pertussis. Other complications in children include neurological complications resulting from hypoxia (i.e. too little oxygen reaching the brain). These include seizures and encephalopathy, especially in infants. Otitis media, anorexia and dehydration are less serious complications. The severe paroxysms can induce pneumothorax, epistaxis, subdural haematomas, hernias and rectal prolapse. More than 80% of deaths from pertussis occur in children less than three months of age. The disease has much less severe outcomes in adolescents and adults, including difficulty in sleeping, urinary incontinence, pneumonia and rib fracture.
The World Health Organisation (WHO) estimates that in 2008, about 16 million cases of pertussis occurred globally, 95% of which were in developing countries, and that about 195 000 children died from the disease. In 2011 this had dropped to 160 000 cases. As vaccination coverage increased, by 2013 the estimated number of deaths globally in <5 year-olds had dropped to 63 000. Between April 2008 and June 2011, 311 laboratory confirmed cases of pertussis were reported in South Africa. The majority were babies too young to be fully vaccinated.
However, these cases are likely to be an underrepresentation of pertussis cases in South Africa, where the true burden of pertussis is unknown. For example, as part of the GERMS-SA project, the NICD coordinates syndromic respiratory illness surveillance using specimens collected from a number of sentinel sites throughout South Africa, which includes testing for pertussis. In 2016, 0.3% of influenzalike illness cases and 1% of severe respiratory illness cases tested positive for pertussis.
Haemophilus influenzae is a pleomorphic gram-negative coccobacillus. It is a facultative anaerobe with six capsular serotypes: a through to f. Serotype b causes most invasive diseases (meningitis and sepsis). Serotype b is commonly referred to as Hib.
Hib enters the body through the nasopharynx. It spreads from person-to-person by direct contact or through respiratory droplets during coughing and sneezing. Organisms colonise the nasopharynx and may remain only transiently or for several months in the absence of symptoms in asymptomatic carriers. In some persons, the organism causes an invasive infection (eg bacteraemia or meningitis). The exact mode of invasion is unknown. People in close contact with patients with Hib disease should receive antibiotic prophylaxis to prevent them from getting the disease, and causing outbreaks of Hib disease.
High risk groups include children younger than 5 years; adults older than 65 years; those with poor socio-economic status; those with chronic diseases, including immune deficiency and sickle cell anaemia; those living in overcrowded conditions; and smokers and those living with smokers
Hib disease causes different symptoms depending on which part of the body is affected. The most common severe types of Hib diseases are: pneumonia (lung infection); bacteremia (bloodstream infection); and meningitis (infection of the covering of the brain and spinal cord). Meningitis is the most common clinical manifestation of invasive Hib disease, accounting for 50%–65% of cases in the prevaccine era. Epiglottitis (inflammation if the epiglottis) incidence has dropped drastically since the introduction of the Hib vaccine. It is now generally seen only in non-immunized people. Osteomyelitis (bone infection) and pericarditis (infection of the sac covering the heart) are less common forms of invasive Hib disease.
All types of invasive Hib infection may result in death. Also, Hib meningitis may result in brain damage or hearing loss, while Hib bacteremia can result in loss of limbs. When Hib causes a non-invasive infection, like bronchitis or an ear infection, complications are rare and typically not severe.
Before the introduction of the Hib vaccine, 0.5-3% of children and infants carried Hib. In the year 2000, before Hib vaccine use became widespread in the developing world, more than 8 million under 5 year-olds globally suffered from invasive Hib disease. By 2013, the vaccine was included in the national immunisation programmes of 184 countries, which saw a greater than 90% reduction in invasive Hib disease.
In 1992, seven years before South Africa introduced Hib vaccination into the EPI, 169 per 100 000 under one year-olds suffered invasive Hib infections. This dropped to 14 per 100 000 by the year 2000, a year after the vaccine was introduced. Thanks to vaccination against Hib, by the end of 2015 respiratory illness surveillance carried out by the GERMS-SA project found that serotype b was no longer the predominant Haemophilus influenzae strain causing invasive disease in South African children, with the biggest statistically significant decline being seen in under one year-old children. In addition, most of the invasive Hib cases that occurred in 2015 were in unvaccinated children, which again illustrates the importance of ensuring that all children receive age-appropriate timely vaccination, and that Road to Health Cards are checked to avoid missed vaccination opportunities.
In 2000, before Hib vaccine use became widespread in the developing world, over 370 000 under 5 year-olds globally died from Hib disease. By 2008, with more widespread use of the vaccine in the developing world, this was reduced to 203 000 deaths. In South Africa, the case fatality rate has remained at 16%, pre- and post-vaccination introduction, thus since the number of cases has drastically reduced, so has the number of deaths.
The causative agent of IPD is the bacterium Streptococcus pneumoniae (known as the pneumococcus). It is a facultative anaerobe, and being a gram positive diplococcus, microscopically it is shaped like a lancet. There are more than 90 known serotypes based on their reaction with type-specific antisera. The organism is encapsulated, with the capsule being its most important virulence factor. Pneumococcus is a leading cause of serious illness, including bacteraemia, meningitis, and pneumonia among children and adults worldwide
Pneumococci are common inhabitants of the respiratory tract thus autoinoculation can occur. They are transmitted by direct person-to-person contact via respiratory droplets. The spread of the organism within a family or household is influenced by factors such as overcrowding, and the presence of upper respiratory infections. The period of communicability is unknown.
Infants and the elderly, and those with underlying medical conditions are at high risk of IPD. Conditions that increase the risk of IPD include decreased immune function from disease or drugs. In South Africa, HIV-positive under 1 year-olds are at the highest risk, while HIV-positive 25-44 year-olds are at the second highest risk. Other risk factors include having functional or anatomic asplenia, chronic heart disease, pulmonary diseases including asthma, liver disease, renal disease, and cerebrospinal fluid leak. Cigarette smoking is also a risk factor. Persons with a cochlear implant appear to be at increased risk of pneumococcal meningitis.
The major clinical syndromes of pneumococcal disease are pneumonia, bacteraemia, and meningitis. Symptoms of pneumococcal pneumonia include fever, chills, rigors, chest pain, cough producing mucopurulent, rusty sputum, dyspnea (shortness of breath), tachypnea (rapid breathing), hypoxia (poor oxygenation), tachycardia (rapid heart rate), malaise and weakness. Pneumococcal pneumonia is the most common clinical presentation of pneumococcal disease among adults, although pneumonia alone is not considered to be an “invasive” disease. Symptoms of pneumococcal bacteraemia include fever, headache, aching muscles, tachypnea and tachycardia. Bacteraemia is the most common IPD in children under 2 years of age. The classical symptoms of pneumococcal meningitis are stiff neck, headache and fever. Other symptoms include tiredness, vomiting, irritability, seizures and coma. Pneumococcal infection was the most common cause of bacterial meningitis in South African under one year-olds in 2007.
Complications of pneumococcal pneumonia include empyema, pulmonary abscess, endocarditis, and death. The case fatality rate is 5-7%, but can be much higher in the elderly. Pneumococcal meningitis has a case fatality rate in adults and children of 22% and 8% respectively. Neurological sequelae are common in survivors. Pneumococcal bacteraemia has an overall case-fatality rate of 20%. In elderly patients this can reach 60%, and can be even higher in asplenic patients. Slide 49: In 2000, the year that the first pneumococcal conjugate vaccine (PCV7) was first licenced in developed countries for use in infant immunisation programmes, there were an estimated 14·5 million IPD cases in under 5 year-olds globally, resulting in 826 000 deaths, with 91 000 being HIV-positive and 735 000 being HIV-negative. The majority (61%) of the deaths in HIV-negative children occurred in ten African and Asian countries. Slide 50: Following the introduction of PCV7 in 2000, dramatic declines in IPD were reported among under 5 year-olds as early as 2001 in the USA. Herd immunity also resulted from the use of PCV7, since there was a reduction in IPD among older children and adults, through reduced transmission of vaccine serotype pneumococci. Serotype replacement resulted in a small increase in IPD caused by serotypes not included in PCV7, a problem that was addressed by introducing PCV13 in 2010.
In South Africa, 70% of IPD cases occur in HIV-infected children. In 2008, the year before the introduction of PCV7 in South Africa, the incidence of IPD was 6-fold higher in under 1 year-olds compared to children 1–4 years of age: 87 per 100 000 and 14 per 100 000, respectively. PCV7 was replaced by PCV13 in 2011, and by 2012, there had been a 69% decline of IPD in under 2 year-olds, and a 34% decline in IPD in 25-44 year-olds, when comparing the pre-vaccine to the post-vaccine era. The latest GERMS-SA report shows that the overall incidence of IPD dropped to 5.06 per 100 000 in 2014, and 4.8 per 100 000 in 2015.
The full name for polio is poliomyelitis. The name is derived from the Greek words “polio” (grey) and “myelon” (marrow, which was equated with the spinal cord). Polio is caused by the poliovirus, which is an enterovirus (viruses that enter the body through the gastrointestinal tract) belonging to the family Picornaviridae (from “small=pico”, “RNA”, “virus”).
The poliovirus has a RNA genome, and there are three serotypes (P1, P2 and P3). The immunity produced by infection with one serotype does not provide good immunity against infection with the other serotypes. Wild (i.e. naturally occurring, not the vaccine strain) P2 has been eradicated globally by vaccination, while wild P3 has not been detected since November 2012, so it is likely that it has also been eradicated.
Polioviruses only infect humans, entering the body through the mouth, and gaining access to cells in the gastrointestinal tract and local lymphoid tissues, where they replicate. Thereafter they enter the bloodstream where they are transported throughout the body. They then infect the cells of the central nervous system where further replication ensues. Cell destruction follows, resulting in paralysis.
The poliovirus is spread mainly via the faecal-oral route. There have been some reports of oral-oral transmission (via respiratory secretions or saliva) during the incubation period as well. Person-to-person spread accounts for the vast majority of transmissions, since the virus does not survive easily outside of the human body, being easily killed by ultraviolet light. In countries where environmental surveillance for polio is conducted, viable polioviruses have been found in sewerage systems, but since they are easily killed by chlorine, drinking water recycled from sewerage is unlikely to be a source of transmission. Heat and formaldehyde can also be used to inactivate the poliovirus. The basic case reproduction number (R0) (average number of successful transmissions in a totally susceptible population) for polio is 5-7, indicating that the poliovirus is highly infectious. Infected children and adults have been shown to transmit the virus to 100% and over 90% respectively, of their susceptible household contacts. The most infectious period is 10 days on either side of the onset of symptoms. However, while the virus starts disappearing from the throat about one week after the onset of symptoms, it can still be shed in stools for up to six weeks thereafter.
Polio affects all susceptible people of all ages. However, adults are more likely to have more severe symptoms, and are also more likely to become paralysed and die. Specific groups at high risk for polio infection include all unimmunised household contacts of infected people, unimmunised healthcare workers who come into contact with patient stools, and unimmunised travellers to polio endemic countries.
The incubation period ranges from 3 to 35 days, but on average is 6 to 20 days. This is followed by one of several different types of clinical presentation. More than 90% of infections are asymptomatic / inapparent, but asymptomatic people are infectious as they harbour virus in their throats and shed virus in their stools. Between 4 to 8% of infections result in “abortive polio”, with patients recovering completely within a week. There is no evidence of central nervous system invasion, and symptoms are those of a minor, nonspecific illness. These include three syndromes: sore throat and fever similar to other upper respiratory tract viral infections; symptoms of gastrointestinal infection such as nausea, vomiting, abdominal pain, constipation or sometimes diarrhoea; and influenza-like symptoms.
Between 1 to 2% of infections result in a prodrome of minor, non-specific illness for several days, followed by nonparalytic aseptic meningitis, characterised by abnormal sensations and stiffness of the neck, back, and/or legs. Complete recovery usually follows when symptoms disappear 2 to 10 days from onset. Acute flaccid (floppy) paralysis (AFP) occurs in less than 1% of polio infections. A prodrome of minor, non-specific illness for 1 to 10 days is followed by fever and paralytic symptoms that progress for 2 to 3 days. Children sometimes experience a biphasic prodrome, with minor symptoms appearing in the first phase and major symptoms appearing in the second. These include loss of superficial reflexes, severe muscle aches and spasms in the limbs or back. Thereafter flaccid paralysis sets in. AFP is a notifiable condition in South Africa, and all AFP cases must be investigated for polio. AFP surveillance is a very important part of polio eradication
Flaccid paralysis / paralytic polio outcomes are determined by the site and degree of central nervous system cell destruction. Spinal polio is the most common (almost 80%), resulting from destruction of anterior horn or ventral grey matter cells of the spinal cord. Asymmetric paralysis involving the legs is the most common outcome of spinal polio.
Bulbospinal or respiratory polio is a combination of bulbar and spinal polio, and is the second most common type of polio (19%). Paralysis of the diaphragm results from destruction of the nerve cells of the cervical spinal cord, and breathing is difficult. Patients die if not supported by a ventilator.
Bulbar polio is the least common (2%), resulting from destruction of nerve cells in the bulbar region of the brain stem. Muscles innervated by cranial nerves are affected, leading to difficulties with breathing, swallowing and speaking. Death occurs from suffocation, pulmonary oedema and shock. The risk of dying from paralytic polio increases with age, with death resulting in 2 to 5% of children and 15 to 30% of adults (depending on age). In the case of bulbar and bulbospinal polio, the death rate increases to 25 to 75%. Recovery from paralytic polio is common, with muscle function returning to some degree in most patients. If weakness or paralysis persists for 12 months after onset, then it is usually permanent. Post-polio syndrome (which is not infectious) occurs in 25-40% of adults who survived childhood paralytic polio infections. This includes new muscle pain, new or increased weakness or paralysis, occurring 30 to 40 years post infection.
Polio used to be a global problem with a huge impact on public health, but since the introduction of the first vaccines in 1955 and 1963, it has been successfully eliminated from most countries in the world. This success is thanks mainly to a resolution to eradicate polio passed by the World Health Assembly in 1988, and more recently to the Global Polio Eradication Initiative. In 2015 there were only 74 cases globally, occurring in two endemic countries (Pakistan and Afghanistan), with Nigeria being polio-free since July 2014.
In 2016 there were 37 wild type polio cases, and unfortunately four of them were in Nigeria, thus polio elimination status for the WHO Afro Region has not yet been achieved. Up until the 15th June 2017, there have been 5 cases of wild type polio, and 6 cases of circulating vaccine derived polio virus paralysis. Thus far in 2017, polio remains endemic only in Afghanistan and Pakistan, with respectively 3 and 2 wild type poliovirus cases.
Hepatitis means “inflammation of the liver”. There are several causes of hepatitis, including a number of unrelated viruses. Hepatitis B is one of the most serious types of viral hepatitis with the highest public health impact globally, and is caused by infection with the hepatitis B virus (HBV). HBV is a small DNA virus with a partially double-stranded genome, belonging to the family Hepadnaviridae (from “liver = hepa” “DNA” “virus”).
Humans are the only natural hosts of HBV, although other primates have been infected during laboratory experiments. HBV is hepatotropic, meaning that it infects the liver cells, where it undergoes replication. HBV is not confined to the liver of infected people, but is also found in their blood and body fluids. The surface antigen of HBV (HBsAg) is a non-infectious particle of HBV that is made in excess during viral replication, but as it is also present on the surface of the infectious virus particle, a person who is HBsAg positive should be regarded as infectious. HBV is a relatively resilient virus which can remain infectious for up to seven days at room temperature on the surfaces of items contaminated by infected blood or body fluids.
In regions with intermediate to low endemicity, sexual transmission and intravenous drug abuse are the most important routes of transmission. Intermediate endemicity means that HBsAg prevalence is between 2-7%, which includes north Africa, the Middle East, eastern Europe and central Asia. Low endemicity means that HBsAg prevalence is <2%, which includes western Europe, north America and Australia.
In highly endemic (i.e. HBsAg prevalence ≥8%) regions of the world (which includes subSaharan Africa and parts of Asia), most HBV transmission occurs during early childhood. In sub-Saharan Africa, the predominant route of transmission is horizontal between toddlers (i.e. transmission unrelated to recognised sexual, perinatal, or parenteral exposure), while in southeast Asia the predominant route is perinatal. Sexual transmission and parenteral (i.e. via intravenous, intramuscular or subcutaneous routes) transmission are other important routes of transmission in these regions, but since most people have been exposed to HBV in childhood and are thus either immune or chronically infected by the time they reach sexual maturity, these routes are less important.
South Africa is highly endemic for HBV, and as in other sub-Saharan African countries, horizontal transmission between toddlers is the most important transmission route. Ritual scarification, weeping sores and saliva (eg: when toddlers bite each other) have all been implicated in horizontal transmission among toddlers.
HBV is highly infectious – it is 100 times more infectious than HIV. An infected person is infectious whenever HBV DNA is present in their blood, regardless of whether or not they are symptomatic. While HBsAg is commonly used as a marker of infectivity, patients with HBV/HIV coinfections are often HBsAg negative. Patients with acute symptomatic hepatitis B are regarded as infectious two months on either side of onset of symptoms
Populations at risk differ according to regions of HBV endemicity and predominant mode of transmission in the region. For example, because HBV is a blood-borne disease, globally all healthcare workers performing invasive procedures or working with body fluids are at risk for exposure to HBV. However, clearly those healthcare workers working in regions of low HBV endemicity are at a lower risk than those working in regions of high endemicity. Broadly speaking, the following populations are at high risk for HBV infection, regardless of the region in which they live: (a) Infants born to mothers who have acute or chronic HBV infections; (b) Children whose siblings, playmates or household contacts are infected with HBV; (c) Adults whose household or sexual contacts are infected with HBV; (d) Institutionalised people (eg: those living in mental institutions; prisoners); (e) Injecting drug abusers; (f) Men who have sex with men; (g) Haemodialysis patients; (h) HIV positive people; and (i) Healthcare workers.
The host’s immune response to HBV is what causes the symptoms of hepatitis B, not the virus itself. This is why infections in infants are mostly asymptomatic, as their immune systems are not well developed so they are not able to mount an immune response. If HBV is not cleared by the host’s immune system, it can remain in the liver (when it is then referred to as chronic hepatitis B) and cause symptoms in later life.
The incubation period is 30 to 180 days, with an average of 75 days. The first symptoms (preicteric phase, meaning the phase before jaundice appears) of hepatitis B include abdominal pain, not feeling well, tiredness, loss of appetite, nausea, vomiting, fever, headache, muscle and joint pain, rash and dark urine. About 3 to 10 days after these symptoms appear, the icteric phase begins. The symptoms seen in this phase include all the pre-icteric symptoms, jaundice, light stools, an enlarged liver, and sometimes an enlarged spleen. This phase persists for up to three weeks, when the convalescent phase begins. As this final phase progresses most of the symptoms disappear, but tiredness and not feeling well may persist for months. Similar symptoms occur in all acute viral hepatitis cases, so one can only diagnose hepatitis B by doing serology tests. These tests are based on the surface antigen of HBV (HBsAg), the host’s non-neutralising antibody produced against the core antigen of HBV (anti-HBc), and the host’s neutralising antibody produced against the HBsAg (anti-HBs, the same antibody induced by vaccination).
About 1% of acute symptomatic HBV infections result in fulminant hepatitis, which has a casefatality rate of between 63 to 93%. The vast majority of acute symptomatic HBV infections generally resolve completely with no long-term sequelae. However, asymptomatic acute infections generally result in chronic HBV infections. The chance of developing chronic HBV infections is inversely related to the age of the host at the time of infection: 90% of infants, 30 to 50% of one to five year-olds, and 5% of adolescents and adults develop chronic HBV infections. Serology tests can be used to differentiate between different stages of HBV infection. A lab result of positivity for HBsAg and anti-HBc, while antiHBs is negative, means that the patient has not yet entered the convalescent phase. The patient might never enter the convalescent phase if their infection is chronic. However, the majority of symptomatic patients with acute hepatitis B do enter the convalescent phase and resolve their infections, which is denoted by the appearance of anti-HBs and the disappearance of HBsAg. Anti-HBs positivity indicates that the person is immune, and this immunity is usually for life. When HBsAg remains positive for more than six months, the patient has a chronic HBV infection. Anti-HBc remains in the blood of anyone who has been infected by HBV, and is thus used as a marker of past or present natural infection.
Chronic HBV infections often have long-term sequelae including chronic hepatitis B, cirrhosis, liver failure and liver cancer. Of those who develop chronic hepatitis B, about 25% will die prematurely from cirrhosis or liver cancer. Globally, about 80% of liver cancers are caused by HBV infection. Globally, more than 2 billion people have been infected by HBV and 360 million are chronically infected. Sub-Saharan Africa is a region that is highly endemic for HBV (i.e. ≥8% of the population are HBsAg positive), and at least 65 million are chronically infected. Before the introduction of the HB vaccine into EPI-SA in 1995, South Africa had a HBsAg prevalence of about 10% in the Black population, with HBV being responsible for 60% of the acute viral hepatitis cases and 90% of the liver cancer cases in the country. A recent study comparing a pre-vaccine era to a post-vaccine era population, found a 60% reduction in chronic HBV infection. About 25% of people with chronic HBV infections will die from long-term outcomes such as cirrhosis and liver cancer. Based on data from 2000, the WHO estimated that globally, approximately 600 000 people die from acute and chronic HBV infections every year. Although hepatitis B is a notifiable disease in South Africa and the underlying causes of deaths from liver cancers are supposed to be recorded in the National Cancer Registry, the data on hepatitis B are very poor and unreliable.
Measles is caused by a highly contagious virus called measles virus, an RNA virus in the family Paramyxovirus. Measles virus infects alveolar macrophages and dendritic cells in the lungs. These cells transport the virus to regional lymph nodes where T and B cells become infected. Other body sites such as the spleen, lymphatic tissue, liver, thymus, and skin also become infected. Infection of dermal capillary endothelial cells and immune complex formation lead to the development of the characteristic skin rash
Measles is a respiratory infection which spreads through coughs and sneezes of infected persons. It may also be spread through contact with saliva or nasal secretions. Transmission can happen 4 days before to 4 days after the rash appears. It is most infectious during the early symptom period (3- 7 days before rash) and at the time the rash appears. Measles is a highly communicable disease. The basic case reproduction number (R0) (average number of successful transmissions in a totally susceptible population) for measles is 12-18, indicating that measles is exceptionally highly infectious. Nine out of ten of an infected person’s household contacts who are not immune will be infected with measles.
Infants are generally protected by maternal antibodies until they are at least 6 months old, thus all unvaccinated people older than 6 months are at risk of infection. Because the vaccine is not 100% effective and measles is highly infectious, vaccinated people who regularly come into contact with unvaccinated children are also at risk of infection. This includes school children, college/university students, international travelers, healthcare workers, and those living or working in overcrowded conditions. Those at high risk for complications include children under 5 years of age, adults who are 20 years and older, pregnant women, people with underlying immunodeficiency, malnourished children and those with vitamin A deficiency.
The symptoms of measles begin about 7 to 18 days after infection. First symptoms include fever, coryza (runny nose), hacking cough, and red eyes which are sometimes sensitive to bright light. Koplik's spots (tiny white spots) appear inside the mouth 2 to 4 days later, and then a sore throat develops. The characteristic rash appears 3 to 5 days after the start of symptoms. The rash begins in front and below the ears and on the side of the neck as irregular, flat, red areas that soon become raised. The rash spreads within 1 to 2 days to the body and begins to fade on the face, lasting 4-7 days.
At the peak of the illness, the child feels very sick and develops eye inflammation (conjunctivitis), the rash is extensive, as can be seen in this slide, and the temperature may exceed 40° C. Diarrhoea is the most common complication of measles (occurring in 8% of cases), especially in young children. Secondary bacterial infections occur quite often, such as middle ear infection (otitis media, occurring in 7% of cases), or pneumonia (occurring in 6% of cases). Pneumonia can be fatal, and is the most common cause of measles-related death, accounting for about 60% of deaths. Brain infection (encephalitis) occurs in about 0.1% of cases, and has a 15% case-fatality rate, with 25% of survivors having permanent neurological damage. Measles outcomes in developing countries are more severe, with up to 25% case fatality rates. Measles is one of the leading causes of blindness in African children.
In rare cases, measles persists in the brain, resulting in subacute sclerosing panencephalitis (SSPE) months to years later, resulting in brain damage and death. This slide shows a young woman who recovered well from measles infection as a child, but developed SSPE as a young adult, and is now completely disabled. The only World Health Organization Region to ever have eliminated measles is the Americas. However the USA has been experiencing a resurgence of measles cases for the past number of years, because of anti-vaccination lobbying. In 2016, 189 230 measles cases globally were reported to the World Health Organization. The USA was among the 25% of countries with between 10 to 99 cases occurring between 1 September 2016 to 28 February 2017, as was South Africa.
The last major measles outbreak in South Africa was from January 2009 to May 2011, with 18 434 confirmed cases. We are however currently experiencing a measles outbreak in South Africa, with 60 cases reported up to the 23rd May. The first outbreak started on the 16th January in the Western Cape, with 29 cases by the 14th March. The first case from Gauteng was reported in January, followed by the next case being reported in March, with 24 cases being reported by 23rd May. In addition, 4 cases were reported in Northwest Province, and 1 case each was reported in Mpumalanga, Eastern Cape and Limpopo Province. In 2013, 2014 and 2015, the WHO estimated that there were respectively 145 700, 114 900 and 134 200 measles deaths globally, which is 314 to 400 deaths every day or 13 to 16 deaths every hour. Most of these deaths occurred in under 5 year-olds in developing countries.
In 1973, using an electron microscope, Bishop and colleagues discovered a virus particle in the intestinal tissue of children with diarrhoea. This virus was subsequently named “rotavirus” because it resembled a wheel (‘rota’ is Latin for wheel). Subsequent studies confirmed that rotavirus is the most common cause of severe gastroenteritis in infants and young children below the age of five years globally. Rotavirus is a double-stranded RNA virus belonging to the family Reoviridae. Eight groups of rotaviruses (group A to H) have been identified, with group A being the most common species and causing more than 90% of all rotavirus infections in humans.
The major mode of transmission of rotaviruses is the faecal-oral route through contact with polluted/contaminated surfaces. The respiratory route may also be a possible route of transmission. The stool of an infected person can contain more than 10 trillion infectious particles per gram, and only less than 100 particles are required to cause infection after person-to-person transmission. Large quantities of virus are shed in the stool from 2 days before diarrhoea onset to 10 days after onset. Rotavirus can be detected in the stools of immuno-deficient persons for more than 30 days after infection.
Rotaviruses are highly communicable and very stable in the environment, being able to survive between 9 and 19 days in open air. Hygiene measures suitable for eliminating bacteria and parasites seem to be ineffective in the control of rotavirus. The incidence of rotavirus infection in countries with high and low health standards is the same, with every child being infected by rotavirus before the age of 5 years irrespective of social class, hence the name “democratic virus”. It is commonly spread within families, institutions, hospitals, and child care settings such as crèches.
Everyone can get rotavirus infection, but infants and children under the age of 5 are most at risk for severe disease. Children in developing countries where oral rehydration solutions are not readily available, are at high risk for dehydration and death from rotavirus diarrhoea. Congenital immunodeficiency and bone marrow or solid organ transplantation are risk factors for severe or prolonged rotavirus gastroenteritis
The incubation period for rotavirus disease is approximately two days. The disease is characterised by vomiting and watery diarrhoea for three to eight days. Fever, with up to a third of infected children having temperatures exceeding 39°C, and abdominal pain also frequently occur. Additional symptoms include loss of appetite and dehydration. Symptoms of dehydration include a decrease in urination, dry mouth and throat, and feeling dizzy when standing up. A dehydrated child may also cry with few or no tears and is unusually sleepy or fussy. The first infection (usually after three months of age) is generally the most severe. Infection may also be asymptomatic, or may cause self-limiting watery diarrhoea. Vaccinated and unvaccinated children may develop rotavirus disease more than once because neither vaccine nor natural infection provides full immunity (protection) from future infections. The stool characteristics of rotavirus diarrhoea are nonspecific, and a similar illness may be caused by other diarrhoeal pathogens. Thus confirmation of a diarrheal illness as rotavirus infection requires laboratory testing.
Globally, over 3 million new diarrhoea cases annually are due to rotavirus, more than 2 million children are hospitalised and more than 25 million clinic visits are made each year costing every country millions of dollars in loss of revenue to lost working hours and hospital expenses. In South Africa, 23- 25% of total hospital admissions were due to diarrhoeal disease before the introduction of rotavirus vaccines into the EPI, with 17-23 % of these cases being positive for rotavirus. The incidence of rotavirus infection is highest during the cool, dry winter months, peaking at 56% during May (the start of the South African winter).
Globally, rotavirus induced gastroenteritis is estimated to cause approximately 450 000 deaths in children below 5 years of age. Over 50% of these deaths occur in Africa, with sub-Saharan Africa having the bulk of the mortality at an estimated 310 000 deaths annually. According to WHO estimates, five African countries recorded the highest rotavirus mortality rates of more than 300 per 100 000 children less than 5 years of age. In South Africa, before the introduction of rotavirus vaccination into the immunisation programme, approximately 320 deaths per 100 000 under 5 year-olds (i.e. 24% of deaths among children aged 1–5 years) were due to rotavirus diarrhoea annually.