Leptospirosis
Leptospirosis is an infectious disease caused by bacteria belonging to the genus Leptospira. Leptospirosis occurs worldwide, but is most prevalent in tropical and subtropical regions. Outbreaks can occur following excessive rainfall or flooding.

Etiology
Virtually all wild and domestic mammals can harbour the bacteria that cause leptospirosis in their kidneys and genital tracts and act as source of infection to humans and other animals.
• Rodents were the first recognized carriers of leptospirosis and are considered the primary source of infection to human beings.
• Cattle, buffaloes, horses, sheep, goat, pigs and dogs are also considered common reservoirs of the bacteria that causes leptospirosis.

Pathophysiology
• Leptospirosis can be transmitted to humans through cuts and abrasions of the skin, or through the mucous membranes of the eyes, nose and mouth with water contaminated with the urine of infected animals. As animals are constantly in our environment, there is a particular danger of getting leptospirosis when flooding occurs, such as following a typhoon or very heavy seasonal rains, because of exposure to contaminated water when wading in floodwaters.
• Leptospirosis can occasionally also be transmitted through the drinking of water or ingestion of food contaminated with urine of infected animals, often rats.
• Human-to-human transmission occurs only very rarely.

Risk Factors
Outbreaks of leptospirosis have been reported following natural disasters such as flooding. The risk of infection depends on exposure. Some humans have a high risk of exposure because of their occupation, the environment they live in or their lifestyle.
The main occupational groups at risk include:
• farm and agricultural workers
• pet shop workers
• veterinarians
• sewer workers
• abattoir workers
• meat handlers
• military personnel
• survivors of natural disasters (e.g., flooding)
• people engaging in recreational water sports (swimming, etc)
In some countries, practically the whole population is at risk as a result of high exposure to contaminated water in daily activities, e.g. working in paddies and sugarcane plantations. The number of males with leptospirosis is often higher than that of females. This may reflect occupational exposure in male dominated activities.
Although leptospirosis is often considered to be a rural disease, people living in cities may also be at risk, because of exposure to infected rats.

Signs and Symptoms
The incubation period of leptospirosis is usually 5–14 days, with a range of 2–30 days. The symptoms following infection with leptospira can vary from a mild 'flu'-like illness to a serious and sometimes fatal disease.
Leptospirosis is often difficult to diagnose clinically, as it can appear to be very similar to many other diseases such as dengue, typhoid and viral hepatitis. Although the disease is a self-limiting and often clinically inapparent illness in the majority of cases, 5-15% of untreated cases can progress to a more severe and potentially fatal stage.

Management
Treatment
Leptospirosis can be treated with antibiotics that should be given as early in the course of illness as possible. If you have symptoms of leptospirosis and have been exposed to water potentially contaminated with urine of infected animals, consult a doctor. If leptospirosis is suspected, appropriate antibiotics will be prescribed. Treatment is most effective when started as soon as possible. Clinicians should never wait for the results of laboratory tests before starting treatment with antibiotics.

Prevention
Risk of infection is minimized by avoiding contact with animal urine, infected animals or a contaminated environment.
Measures to prevent transmission of leptospirosis include the following:
• Wearing protective clothing (boots, gloves, spectacles, aprons, masks).
• Covering skin lesions with waterproof dressings.
• Preventing access to, or giving adequate warning about water bodies known or suspected to be contaminated (pools, ponds, rivers). Try to avoid wading or swimming in potentially contaminated water.
• Washing or showering after exposure to urine splashes or contaminated soil or water.
• Washing and cleaning wounds.
• Avoiding or preventing urine splashes and aerosols, avoiding touching ill or dead animals, or assisting animals in giving birth.
• Strictly maintaining hygienic measures during care or handling all animals.
• Where feasible, disinfecting contaminated areas (scrubbing floors in stables, butcheries, abattoirs, etc.).
• Consuming clean drinking-water.
Although human vaccines have been used in some countries with varying degrees of success, there are no WHO pre-qualified vaccines currently available.

Meningococcal meningitis
• Meningococcal meningitis is a bacterial form of meningitis, a serious infection of the thin lining that surrounds the brain and spinal cord.
• The meningitis belt of sub-Saharan Africa, stretching from Senegal in the west to Ethiopia in the east, has the highest rates of the disease.
• Group A meningococcus accounts for an estimated 80–85% of all cases in the meningitis belt, with epidemics occurring at intervals of 7–14 years.
• In the 2009 epidemic season, 14 African countries implementing enhanced surveillance, reported 88 199 suspected cases, including 5352 deaths, the largest number since a 1996 epidemic.
• Several vaccines are available to control the disease: a meningococcal A conjugate vaccine, C conjugate vaccines, tetravalent A, C, Y and W135 conjugate vaccines and meningococcal polysaccharide vaccines.
Meningococcal meningitis is a bacterial form of meningitis, a serious infection of the meninges that affects the brain membrane. It can cause severe brain damage and is fatal in 50% of cases if untreated.
Etiology
Several different bacteria can cause meningitis. Neisseria meningitidis is the one with the potential to cause large epidemics. Twelve serogroups of N. meningitidis have been identified, six of which (A, B, C, W135, X and Y) can cause epidemics. Geographic distribution and epidemic potential differ according to serogroup.
Pathophysiology
The bacteria are transmitted from person-to-person through droplets of respiratory or throat secretions from carriers. Close and prolonged contact – such as kissing, sneezing or coughing on someone, or living in close quarters (such as a dormitory, sharing eating or drinking utensils) with an infected person (a carrier) – facilitates the spread of the disease. The average incubation period is four days, but can range between two and 10 days.
Neisseria meningitidis only infects humans; there is no animal reservoir. The bacteria can be carried in the throat and sometimes, for reasons not fully understood, can overwhelm the body's defenses allowing infection to spread through the bloodstream to the brain. Although there remain gaps in our knowledge, it is believed that 10% to 20% of the population carries Neisseria meningitidis in their throat at any given time. However, the carriage rate may be higher in epidemic situations.
Prevalence
Meningococcal meningitis occurs in small clusters throughout the world with seasonal variation and accounts for a variable proportion of epidemic bacterial meningitis.
The largest burden of meningococcal disease occurs in an area of sub-Saharan Africa known as the meningitis belt, which stretches from Senegal in the west to Ethiopia in the east. During the dry season between December to June, dust winds, cold nights and upper respiratory tract infections combine to damage the nasopharyngeal mucosa, increasing the risk of meningococcal disease. At the same time, transmission of N. meningitidis may be facilitated by overcrowded housing and by large population displacements at the regional level due to pilgrimages and traditional markets. This combination of factors explains the large epidemics which occur during the dry season in the meningitis belt.
Signs and Symptoms
The most common symptoms are a stiff neck, high fever, sensitivity to light, confusion, headaches and vomiting. Even when the disease is diagnosed early and adequate treatment is started, 5% to 10% of patients die, typically within 24 to 48 hours after the onset of symptoms. Bacterial meningitis may result in brain damage, hearing loss or a learning disability in 10% to 20% of survivors. A less common but even more severe (often fatal) form of meningococcal disease is meningococcal septicaemia, which is characterized by a haemorrhagic rash and rapid circulatory collapse.
Management
Diagnosis
Initial diagnosis of meningococcal meningitis can be made by clinical examination followed by a lumbar puncture showing a purulent spinal fluid. The bacteria can sometimes be seen in microscopic examinations of the spinal fluid. The diagnosis is supported or confirmed by growing the bacteria from specimens of spinal fluid or blood, by agglutination tests or by polymerase chain reaction (PCR). The identification of the serogroups and susceptibility testing to antibiotics are important to define control measures.
Treatment
Meningococcal disease is potentially fatal and should always be viewed as a medical emergency. Admission to a hospital or health centre is necessary, although isolation of the patient is not necessary. Appropriate antibiotic treatment must be started as soon as possible, ideally after the lumbar puncture has been carried out if such a puncture can be performed immediately. If treatment is started prior to the lumbar puncture it may be difficult to grow the bacteria from the spinal fluid and confirm the diagnosis.
A range of antibiotics can treat the infection, including penicillin, ampicillin, chloramphenicol and ceftriaxone. Under epidemic conditions in Africa in areas with limited health infrastructure and resources, oily chloramphenicol or ceftriaxone are the drugs of choice because a single dose has been shown to be effective on meningococcal meningitis.
Prevention
There are three types of vaccines available.
1. Polysaccharide vaccines have been available to prevent the disease for over 30 years. Meningococcal polysaccharide vaccines are available in either bivalent (groups A and C), trivalent (groups A, C and W), or tetravalent (groups A, C, Y and W135) forms to control the disease.
2. For group B, polysaccharide vaccines cannot be developed, due to antigenic mimicry with polysaccharide in human neurologic tissues. Consequently, vaccines against B used in particular in Cuba, New Zealand and Norway were outer membrane proteins (OMP) and strain-specific to control specific epidemics. Additional universal group B protein vaccines are in late stages of development.
3. Since 1999, meningococcal conjugate vaccines against group C have been available and widely used. Tetravalent A, C, Y and W135 conjugate vaccines have been licensed since 2005 for use in children and adults in Canada, the United States of America, and Europe.
In December 2010, a new meningococcal A conjugate vaccine was introduced nationwide in Burkina Faso, and in selected regions of Mali and Niger, with a total of 20 million persons 1 to 29 years of age vaccinated. Subsequently these countries reported, in 2011, the lowest number of confirmed meningitis A cases ever recorded during an epidemic season. Between October and December 2011, another 35 million persons were immunized across Mali and Niger ― both countries have completed their nationwide campaigns ― and three countries Cameroon, Chad and Nigeria launched their national campaigns. Four countries in the African meningitis belt are preparing for introduction of the vaccine in 2012 Benin, Ghana, Senegal and Sudan; while Cameroon, Chad and Nigeria are pursuing their nationwide campaigns.
The vaccine has several advantages over existing polysaccharide vaccines: it induces a higher and more sustainable immune response against group A meningococcus; it reduces the carriage of the bacteria in the throat and thus its transmission; it is expected to confer long-term protection not only for those who receive the vaccine, but on family members and others who would otherwise have been exposed to meningitis; it is available at a lower price than other meningococcal vaccines; and it is expected to be particularly effective in protecting children under two years of age, who do not respond to conventional polysaccharide vaccines.
It is hoped that all 26 countries in the African meningitis belt will have introduced this vaccine by 2016. High coverage of the target age group of 1–29 years is expected to eliminate meningococcal A epidemics from this region of Africa.
Global public health response
With the introduction of the new meningococcal A conjugate vaccine, WHO promotes a strategy comprising epidemic preparedness, prevention and response. Preparedness focuses on surveillance, from case detection to investigation and laboratory confirmation. Prevention consists of vaccinating all 1-29 year-olds in the African meningitis belt with this vaccine. WHO regularly provides technical support at the field level to countries facing epidemics.
Epidemic response consists of prompt and appropriate case management with oily chloramphenicol or ceftriaxone and reactive mass vaccination of populations not already protected through vaccination.
Meningitis epidemics in the African meningitis belt constitute an enormous public health burden. WHO is committed to eliminating meningococcal disease as a public health problem.

Lassa fever
Lassa fever is an acute viral haemorrhagic illness caused by Lassa virus, a member of the arenavirus family of viruses. It is transmitted to humans from contacts with food or household items contaminated with rodent excreta. The disease is endemic in the rodent population in parts of West Africa. Person-to-person infections and laboratory transmission can also occur, particularly in the hospital environment in the absence of adequate infection control measures. Diagnosis and prompt treatment are essential.
Epidemiology and Pathophysiology
Mastomys natalensis, the natural reservoir of the Lassa fever virus
Lassa virus is zoonotic (transmitted from animals), in that it spreads to humans from rodents, specifically multi-mammate rats (Mastomys natalensis). This is probably the most common rodent in equatorial Africa, ubiquitous in human households and eaten as a delicacy in some areas. In these rats infection is in a persistent asymptomatic state. The virus is shed in their excreta (urine and feces), which can be aerosolized. In fatal cases, Lassa fever is characterized by impaired or delayed cellular immunity leading to fulminant viremia.
Infection in humans typically occurs by exposure to animal excrement through the respiratory or gastrointestinal tracts. Inhalation of tiny particles of infective material (aerosol) is believed to be the most significant means of exposure. It is possible to acquire the infection through broken skin or mucous membranes that are directly exposed to infective material. Transmission from person to person has also been established, presenting a disease risk for healthcare workers. Frequency of transmission via sexual contact has not been established.
Prevalence
The dissemination of the infection can be assessed by prevalence of antibodies to the virus in populations of:
• Sierra Leone 8–52%
• Guinea 4–55%
• Nigeria approx. 21%
Lassa fever is a viral hemorrhagic fever in West Africa. Studies show up to half a million cases of Lassa fever per year in West Africa, with about 5,000 resulting in death. Lassa virus was detected in 25 of 60 (42%) patients in northern and central Edo. The Lassa Virus affects adults and children alike.
Like other hemorrhagic fevers, Lassa fever can be transmitted directly from one human to another. It can be contracted by an airborne route or with direct contact with infected human blood, urine, or semen. Transmission through breast milk has also been observed.
Signs and Symptoms
In 80% of cases, the disease is asymptomatic, but in the remaining 20%, it takes a complicated course. It is estimated that the virus is responsible for about 5,000 deaths annually. The fever accounts for up to one third of deaths in hospitals within the affected regions and 10 to 16% of total cases.
After an incubation period of six to twenty-one days, an acute illness with multiorgan involvement develops. Non-specific symptoms include fever, facial swelling, and muscle fatigue, as well as conjunctivitis and mucosal bleeding. The other symptoms arising from the affected organs are:
• Gastrointestinal tract
• Nausea
• Vomiting (bloody)
• Diarrhea (bloody)
• Stomach ache
• Constipation
• Dysphagia (difficulty swallowing)
• Hepatitis
• Cardiovascular system
• Pericarditis
• Hypertension
• Hypotension
• Tachycardia (abnormally high heart rate)
• Respiratory tract
• Cough
• Chest pain
• Dyspnoea
• Pharyngitis
• Pleuritis
• Nervous system
• Encephalitis
• Meningitis
• Unilateral or bilateral hearing deficit
• Seizures
Clinically, Lassa fever infections are difficult to distinguish from other viral hemorrhagic fevers such as Ebola and Marburg, and from more common febrile illnesses such as malaria.
The virus is excreted in urine for three to nine weeks and in semen for three months.
Managements
Prevention
Control of the Mastomys rodent population is impractical, so measures are limited to keeping rodents out of homes and food supplies, as well as maintaining effective personal hygiene. Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person. These issues in many countries are monitored by a department of public health. In less developed countries these types of organizations may not have the necessary means to effectively control outbreaks.
Researchers at the USAMRIID facility, where military biologists study infectious diseases, have a promising vaccine candidate.They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis virus vectors expressing the Lassa virus glycoprotein. After a single intramuscular injection, test primates have survived lethal challenge, while showing no clinical symptoms.
Diagnosis
There is a range of laboratory investigations that are performed to diagnose the disease and assess its course and complications. ELISA test for antigen and IgM antibodies gives 88% sensitivity and 90% specificity for the presence of the infection. Other laboratory findings in Lassa fever include lymphopenia(low white blood cell count), thrombocytopenia (low platelets), and elevated aspartate aminotransferase (AST) levels in the blood. Lassa fever can also be found in cerebrospinal fluid. In West Africa, where Lassa is most prevalent, it is difficult for doctors to diagnose due to the absence of proper equipment to perform tests. In cases with abdominal pain, diagnoses in endemic countries are often made for other illnesses, such as appendicitis and intussusception, delaying treatment with Ribavirin.
Research has been done in the last few years by a team of specialists in order to diagnose the Lassa fever on a molecular level.
Prognosis
About 15%-20% of hospitalized Lassa fever patients will die from the illness. It is estimated that the overall mortality rate is 1%, however during epidemics mortality can climb as high as 50%. The mortality rate is greater than 80% when it occurs in pregnant women during their third trimester; fetal death also occurs in nearly all those cases. Abortion decreases the risk of death to the mother.
Thanks to treatment with Ribavirin, fatality rates are continuing to decline. Work on a vaccine is continuing, with multiple approaches showing positive results in animal trials.
Treatment
All persons suspected of Lassa fever infection should be admitted to isolation facilities and their body fluids and excreta properly disposed of.
Early and aggressive treatment using Ribavirin was pioneered by Joe McCormick in 1979. After extensive testing, it was determined that early administration is critical to success. Additionally, Ribavirin is almost twice as effective when given intravenously as when taken by mouth. Ribavirin is a prodrug which appears to interfere with viral replication by inhibiting RNA-dependent nucleic acid synthesis, although the precise mechanism of action is disputed. The drug is relatively inexpensive, but the cost of the drug is still very high for many of those in West African states. Fluid replacement, blood transfusion and fighting hypotension are usually required. Intravenous interferon therapy has also been used.
When Lassa fever infects pregnant women late in their third trimester, it is necessary to induce delivery for the mother to have a good chance of survival. This is because the virus has an affinity for the placenta and other highly vascular tissues. The fetus has only a one in ten chance of survival no matter what course of action is taken; hence focus is always on saving the life of the mother. Following delivery, women should receive the same treatment as other Lassa fever patients.
SIGA Technologies is developing an antiviral drug that has been shown effective in treating experimentally infected guinea pigs. In a study conducted at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), treatment with ST-193 once a day for 14 days resulted in significant reduction in mortality (71% of the animals survived at the low dose), whereas all untreated animals and those treated with ribavirin died within 20 days of the infection. Due to threat of disease being used as a potential military weapon, a vaccine to reverse the disease is still being worked on.
As serious as the disease is, there are numerous accounts of survival. However, there have been lasting effects of the disease.