Typhoid fever

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https://en.wikipedia.org/wiki/Typhoid_fever 

 

Typhoid fever
Other names	Enteric fever, slow fever
Causative agent: Salmonella enterica serological variant Typhi (shown under a microscope with flagellar stain)
Specialty	Infectious diseases
Symptoms	Fever that starts low and increases daily, possibly reaching as high as 104.9 °F (40.5 °C) Headache, weakness and fatigue, muscle aches, sweating, dry cough, loss of appetite, weight loss, stomach pain, diarrhea or constipation, rash, swollen stomach (enlarged liver or spleen)
Usual onset	1–2 weeks after ingestion
Duration	Usually 7–10 days after antibiotic treatment begins. Longer if there are complications or drug resistance.
Causes	Gastrointestinal infection of Salmonella enterica serovar Typhi
Risk factors	Living in or travel to areas where typhoid fever is established, Work as a clinical microbiologist handling Salmonella typhi bacteria, Have close contact with someone who is infected or has recently been infected with typhoid fever, Drink water polluted by sewage that contains Salmonella typhi
Prevention	Preventable by vaccine. Travelers to regions with higher typhoid prevalence are usually encouraged to get a vaccination before travel.
Treatment	Antibiotics, hydration, surgery in extreme cases. Quarantine to avoid exposing others (not commonly done in modern times).
Prognosis	Likely to recover without complications if proper antibiotics administered and diagnosed early. If infecting strain is multi-drug resistant or extensively drug resistant then prognosis more difficult to determine. Among untreated acute cases, 10% will shed bacteria for three months after initial onset of symptoms, and 2–5% will become chronic typhoid carriers. Some carriers are diagnosed by positive tissue specimen. Chronic carriers are by definition asymptomatic.

Typhoid fever, also known as typhoid, is a disease caused by Salmonella serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several days. This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting. Some people develop a skin rash with rose colored spots. In severe cases, people may experience confusion. Without treatment, symptoms may last weeks or months. Diarrhea may be severe, but is uncommon. Other people may carry the bacterium without being affected, but they are still able to spread the disease. Typhoid fever is a type of enteric fever, along with paratyphoid fever. S. enterica Typhi is believed to infect and replicate only within humans.

Typhoid is caused by the bacterium Salmonella enterica subsp. enterica serovar Typhi growing in the intestines, peyers patches, mesenteric lymph nodes, spleen, liver, gallbladder, bone marrow and blood. Typhoid is spread by eating or drinking food or water contaminated with the feces of an infected person. Risk factors include limited access to clean drinking water and poor sanitation. Those who have not yet been exposed to the pathogen and ingest contaminated drinking water or food are most at risk for developing symptoms. Only humans can be infected; there are no known animal reservoirs.

Diagnosis is by culturing and identifying S. enterica Typhi from patient samples or detecting an immune response to the pathogen from blood samples. Recently, new advances in large-scale data collection and analysis have allowed researchers to develop better diagnostics, such as detecting changing abundances of small molecules in the blood that may specifically indicate typhoid fever. Diagnostic tools in regions where typhoid is most prevalent are quite limited in their accuracy and specificity, and the time required for a proper diagnosis, the increasing spread of antibiotic resistance, and the cost of testing are also hardships for under-resourced healthcare systems.

A typhoid vaccine can prevent about 40% to 90% of cases during the first two years. The vaccine may have some effect for up to seven years. For those at high risk or people traveling to areas where the disease is common, vaccination is recommended. Other efforts to prevent the disease include providing clean drinking water, good sanitation, and handwashing. Until an infection is confirmed as cleared, the infected person should not prepare food for others. Typhoid is treated with antibiotics such as azithromycin, fluoroquinolones, or third-generation cephalosporins. Resistance to these antibiotics has been developing, which has made treatment more difficult.

In 2015, 12.5 million new typhoid cases were reported. The disease is most common in India. Children are most commonly affected. Typhoid decreased in the developed world in the 1940s as a result of improved sanitation and the use of antibiotics. Every year about 400 cases are reported in the U.S. and an estimated 6,000 people have typhoid. In 2015, it resulted in about 149,000 deaths worldwide – down from 181,000 in 1990. Without treatment, the risk of death may be as high as 20%. With treatment, it is between 1% and 4%.

Typhus is a different disease. Owing to their similar symptoms, they were not recognized as distinct diseases until the 1800s. "Typhoid" means "resembling typhus".

Signs and symptoms

Classically, the progression of untreated typhoid fever has three distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted and emaciated.

• In the first week, the body temperature rises slowly, and fever fluctuations are seen with relative bradycardia (Faget sign), malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. A decrease in the number of circulating white blood cells (leukopenia) occurs with eosinopenia and relative lymphocytosis; blood cultures are positive for S. enterica subsp. enterica serovar Typhi. The Widal test is usually negative.
• In the second week, the person is often too tired to get up, with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave. Delirium can occur, where the patient is often calm, but sometimes becomes agitated. This delirium has given typhoid the nickname "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi (rattling breathing sounds) are heard in the base of the lungs. The abdomen is distended and painful in the right lower quadrant, where a rumbling sound can be heard. Diarrhea can occur in this stage, but constipation is also common. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and liver transaminases are elevated. The Widal test is strongly positive, with antiO and antiH antibodies. Blood cultures are sometimes still positive.
• In the third week of typhoid fever, a number of complications can occur:
  • The fever is still very high and oscillates very little over 24 hours. Dehydration ensues along with malnutrition, and the patient is delirious. A third of affected people develop a macular rash on the trunk.
  • Intestinal haemorrhage due to bleeding in congested Peyer's patches occurs; this can be very serious, but is usually not fatal.
  • Intestinal perforation in the distal ileum is a very serious complication and often fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.
  • Respiratory diseases such as pneumonia and acute bronchitis
  • Encephalitis
  • Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects.
  • Metastatic abscesses, cholecystitis, endocarditis, and osteitis.
  • Low platelet count (thrombocytopenia) is sometimes seen.

Causes

A 1939 conceptual illustration showing various ways that typhoid bacteria can contaminate a water well (center)

Bacteria

The Gram-negative bacterium that causes typhoid fever is Salmonella enterica subsp. enterica serovar Typhi. Based on MLST subtyping scheme, the two main sequence types of the S. Typhi are ST1 and ST2, which are widespread globally. Global phylogeographical analysis showed dominance of a haplotype 58 (H58), which probably originated in India during the late 1980s and is now spreading through the world with multi-drug resistance. A more detailed genotyping scheme was reported in 2016 and is now being used widely. This scheme reclassified the nomenclature of H58 to genotype 4.3.1.

Transmission

Unlike other strains of Salmonella, no animal carriers of typhoid are known. Humans are the only known carriers of the bacterium. S. enterica subsp. enterica serovar Typhi is spread by the fecal-oral route from people who are infected and from asymptomatic carriers of the bacterium. An asymptomatic human carrier is someone who is still excreting typhoid bacteria in stool a year after the acute stage of the infection.

Pathogenesis of typhoid fever

Diagnosis

Diagnosis is made by any blood, bone marrow, or stool cultures and with the Widal test (demonstration of antibodies against Salmonella antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery, or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of the Widal test and blood and stool cultures.

Widal test

Main article: Widal test

 

Widal test card

The Widal test is used to identify specific antibodies in the serum of people with typhoid by using antigen-antibody interactions.

In this test, the serum is mixed with a dead bacterial suspension of salmonella with specific antigens. If the patient's serum contains antibodies against those antigens, they get attached to them, forming clumps. If clumping does not occur, the test is negative. The Widal test is time-consuming and prone to significant false positives. It may also be falsely negative in recently infected people. But unlike the Typhidot test, the Widal test quantifies the specimen with titres.

Rapid diagnostic tests

Rapid diagnostic tests such as Tubex, Typhidot, and Test-It have shown moderate diagnostic accuracy.

Typhidot

Typhidot is based on the presence of specific IgM and IgG antibodies to a specific 50Kd OMP antigen. This test is carried out on a cellulose nitrate membrane where a specific S. typhi outer membrane protein is attached as fixed test lines. It separately identifies IgM and IgG antibodies. IgM shows recent infection; IgG signifies remote infection.

The sample pad of this kit contains colloidal gold-anti-human IgG or gold-anti-human IgM. If the sample contains IgG and IgM antibodies against those antigens, they will react and turn red. The typhidot test becomes positive within 2–3 days of infection.

Two colored bands indicate a positive test. A single control band indicates a negative test. A single first fixed line or no band at all indicates an invalid test. Typhidot's biggest limitation is that it is not quantitative, just positive or negative.

Tubex test

The Tubex test contains two types of particles: brown magnetic particles coated with antigen and blue indicator particles coated with O9 antibody. During the test, if antibodies are present in the serum, they will attach to the brown magnetic particles and settle at the base, while the blue indicator particles remain in the solution, producing a blue color, which means the test is positive.

If the serum does not have an antibody in it, the blue particles attach to the brown particles and settle at the bottom, producing a colorless solution, which means the test is negative.

Prevention

Doctor administering a typhoid vaccination at a school in San Augustine County, Texas, 1943

Sanitation and hygiene are important to prevent typhoid. It can spread only in environments where human feces can come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid. Industrialization contributed greatly to the elimination of typhoid fever, as it eliminated the public-health hazards associated with having horse manure in public streets, which led to a large number of flies, which are vectors of many pathogens, including Salmonella spp. According to statistics from the U.S. Centers for Disease Control and Prevention, the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever.

Vaccination

Two typhoid vaccines are licensed for use for the prevention of typhoid: the live, oral Ty21a vaccine (sold as Vivotif by Crucell Switzerland AG) and the injectable typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline). Both are efficacious and recommended for travelers to areas where typhoid is endemic. Boosters are recommended every five years for the oral vaccine and every two years for the injectable form. An older, killed whole-cell vaccine is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use because it has more side effects (mainly pain and inflammation at the site of the injection).

Vivotif - oral typhoid vaccine of live-attenuated S. enterica Typhi strain Ty21a

To help decrease rates of typhoid fever in developing nations, the World Health Organization (WHO) endorsed the use of a vaccination program starting in 1999. Vaccination has proven effective at controlling outbreaks in high-incidence areas and is also very cost-effective: prices are normally less than US$1 per dose. Because the price is low, poverty-stricken communities are more willing to take advantage of the vaccinations. Although vaccination programs for typhoid have proven effective, they alone cannot eliminate typhoid fever. Combining vaccines with public-health efforts is the only proven way to control this disease.

Since the 1990s, the WHO has recommended two typhoid fever vaccines. The ViPS vaccine is given by injection, and the Ty21a by capsules. Only people over age two are recommended to be vaccinated with the ViPS vaccine, and it requires a revaccination after 2–3 years, with a 55%–72% efficacy. The Ty21a vaccine is recommended for people five and older, lasting 5–7 years with 51%–67% efficacy. The two vaccines have proved safe and effective for epidemic disease control in multiple regions.

A version of the vaccine combined with a hepatitis A vaccine is also available.

Results of a phase 3 trial of typhoid conjugate vaccine (TCV) in December 2019 reported 81% fewer cases among children.

Treatment

Oral rehydration therapy

The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.

Antibiotics

Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin. Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice.  Cefixime is a suitable oral alternative.

Properly treated, typhoid fever is not fatal in most cases. Antibiotics such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin, and ciprofloxacin have been commonly used to treat it. Treatment with antibiotics reduces the case-fatality rate to about 1%.

Without treatment, some patients develop sustained fever, bradycardia, hepatosplenomegaly, abdominal symptoms, and occasionally pneumonia. In white-skinned patients, pink spots, which fade on pressure, appear on the skin of the trunk in up to 20% of cases. In the third week, untreated cases may develop gastrointestinal and cerebral complications, which may prove fatal in 10%–20% of cases. The highest case fatality rates are reported in children under 4. Around 2%–5% of those who contract typhoid fever become chronic carriers, as bacteria persist in the biliary tract after symptoms have resolved.

Surgery

Surgery is usually indicated if intestinal perforation occurs. One study found a 30-day mortality rate of 9% (8/88), and surgical site infections at 67% (59/88), with the disease burden borne predominantly by low-resource countries.

For surgical treatment, most surgeons prefer simple closure of the perforation with drainage of the peritoneum. Small-bowel resection is indicated for patients with multiple perforations. If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is sometimes successful, especially in patients with gallstones, but is not always successful in eradicating the carrier state because of persisting hepatic infection.

Resistance

As resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and streptomycin is now common, these agents are no longer used as first–line treatment of typhoid fever. Typhoid resistant to these agents is known as multidrug-resistant typhoid.

Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia. Many centres are shifting from ciprofloxacin to ceftriaxone as the first line for treating suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand, or Vietnam. Also, it has been suggested that azithromycin is better at treating resistant typhoid than both fluoroquinolone drugs and ceftriaxone. Azithromycin can be taken by mouth and is less expensive than ceftriaxone, which is given by injection.

A separate problem exists with laboratory testing for reduced susceptibility to ciprofloxacin; current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), that isolates sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", and that isolates sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". But an analysis of 271 isolates found that around 18% of isolates with a reduced susceptibility to fluoroquinolones, the class which CIP belongs (MIC 0.125–1.0 mg/L), would not be detected by this method.

Epidemiology

Main article: Epidemiology of typhoid fever

 

Typhoid fever incidence; most common in Asia, Africa, Central and South America

  Strongly endemic areas

  Moderately endemic areas

In 2000, typhoid fever caused an estimated 21.7 million illnesses and 217,000 deaths. It occurs most often in children and young adults between 5 and 19 years old. In 2013, it resulted in about 161,000 deaths – down from 181,000 in 1990. Infants, children, and adolescents in south-central and Southeast Asia have the highest rates of typhoid. Outbreaks are also often reported in sub-Saharan Africa and Southeast Asia. In 2000, more than 90% of morbidity and mortality due to typhoid fever occurred in Asia. In the U.S., about 400 cases occur each year, 75% of which are acquired while traveling internationally.

Before the antibiotic era, the case fatality rate of typhoid fever was 10%–20%. Today, with prompt treatment, it is less than 1%, but 3%–5% of people who are infected develop a chronic infection in the gall bladder. Since S. enterica subsp. enterica serovar Typhi is human-restricted, these chronic carriers become the crucial reservoir, which can persist for decades for further spread of the disease, further complicating its identification and treatment. Lately, the study of S. enterica subsp. enterica serovar Typhi associated with a large outbreak and a carrier at the genome level provides new insight into the pathogenesis of the pathogen.

In industrialized nations, water sanitation and food handling improvements have reduced the number of typhoid cases. Developing nations have the highest rates. These areas lack access to clean water, proper sanitation systems, and proper health-care facilities. In these areas, such access to basic public-health needs is not expected in the near future.

In 2004–2005 an outbreak in the Democratic Republic of Congo resulted in more than 42,000 cases and 214 deaths. Since November 2016, Pakistan has had an outbreak of extensively drug-resistant (XDR) typhoid fever.

In Europe, a report based on data for 2017 retrieved from The European Surveillance System (TESSy) on the distribution of confirmed typhoid and paratyphoid fever cases found that 22 EU/EEA countries reported a total of 1,098 cases, 90.9% of which were travel-related, mainly acquired during travel to South Asia.

Outbreaks

Map of Typhoid Fever Outbreaks 1989–2018

• Plague of Athens (suspected)
• "Burning Fever" outbreak among indigenous Americans. Between 1607 and 1624, 85% of the population at the James River died from a typhoid epidemic. The World Health Organization estimates the death toll was over 6,000 during this time.
• Maidstone, Kent outbreak in 1897–1898: 1,847 patients were recorded to have typhoid fever. This outbreak is notable because it was the first time a typhoid vaccine was deployed during a civilian outbreak. Almoth Edward Wright's vaccine was offered to 200 healthcare providers, and of the 84 individuals who received the vaccine none developed typhoid whereas 4 who had not been vaccinated became ill.
• American army in the Spanish-American war: government records estimate over 21,000 troops had typhoid, resulting in 2,200 deaths.
• In 1902, guests at mayoral banquets in Southampton and Winchester, England, became ill and four died, including the Dean of Winchester, after consuming oysters. The infection was due to oysters sourced from Emsworth, where the oyster beds had been contaminated with raw sewage.
• Jamaica Plain neighborhood, Boston in 1908 - linked to milk delivery. See history section, "carriers" for further details.
• Outbreak in upperclass New Yorkers who employed Mary Mallon - 51 cases and 3 deaths from 1907 to 1915.
• Aberdeen, Scotland, in summer 1964 - traced back to contaminated canned beef sourced from Argentina sold in markets. More than 500 patients were quarantined in the hospital for a minimum of four weeks, and the outbreak was contained without any deaths.
• Dushanbe, Tajikistan, in 1996–1997: 10,677 cases reported, 108 deaths 
• Kinshasa, Democratic Republic of the Congo, in 2004: 43,000 cases and over 200 deaths. A prospective study of specimens collected in the same region between 2007 and 2011 revealed about one third of samples obtained from patient samples were resistant to multiple antibiotics.
• Kampala, Uganda in 2015: 10,230 cases reported

History

Early descriptions

The plague of Athens, during the Peloponnesian War, was most likely an outbreak of typhoid fever. During the war, Athenians retreated into a walled-in city to escape attack from the Spartans. This massive influx of humans into a concentrated space overwhelmed the water supply and waste infrastructure, likely leading to unsanitary conditions as fresh water became harder to obtain and waste became more difficult to collect and remove beyond the city walls. In 2006, examining the remains for a mass burial site from Athens from around the time of the plague (~430 B.C.) revealed that fragments of DNA similar to modern day S. Typhi DNA were detected, whereas Yersinia pestis (plague), Rickettsia prowazekii (typhus), Mycobacterium tuberculosis, cowpox virus, and Bartonella henselae were not detected in any of the remains tested.

It is possible that the Roman emperor Augustus Caesar had either a liver abscess or typhoid fever, and survived by using ice baths and cold compresses as a means of treatment for his fever. There is a statue of the Greek physician, Antonius Musa, who treated his fever.

Definition and evidence of transmission

The French doctors Pierre-Fidele Bretonneau and Pierre-Charles-Alexandre Louis are credited with describing typhoid fever as a specific disease, unique from typhus. Both doctors performed autopsies on individuals who died in Paris due to fever – and indicated that many had lesions on the Peyer's patches which correlated with distinct symptoms before death. British medics were skeptical of the differentiation between typhoid and typhus because both were endemic to Britain at that time. However, in France only typhoid was present circulating in the population. Pierre-Charlles-Alexandre Louis also performed case studies and statistical analysis to demonstrate that typhoid was contagious - and that persons who already had the disease seemed to be protected. Afterward, several American doctors confirmed these findings, and then Sir William Jenner convinced any remaining skeptics that typhoid is a specific disease recognizable by lesions in the Peyer's patches by examining sixty-six autopsies from fever patients and concluding that the symptoms of headaches, diarrhea, rash spots, and abdominal pain were present only in patients who were found to have intestinal lesions after death; these observations solidified the association of the disease with the intestinal tract and gave the first clue to the route of transmission.

In 1847 William Budd learned of an epidemic of typhoid fever in Clifton, and identified that all 13 of 34 residents who had contracted the disease drew their drinking water from the same well. Notably, this observation was two years prior to John Snow discovering the route of contaminated water as the cause for a cholera outbreak. Budd later became health officer of Bristol and ensured a clean water supply, and documented further evidence of typhoid as a water-borne illness throughout his career.

Cause

Polish scientist Tadeusz Browicz described a short bacillus in the organs and feces of typhoid victims in 1874. Browicz was able to isolate and grow the bacilli but did not go as far as to insinuate or prove that they caused the disease.

In April 1880, three months prior to Eberth's publication, Edwin Klebs described short and filamentous bacilli in the Peyer's patches in typhoid victims. The bacterium's role in disease was speculated but not confirmed.

In 1880, Karl Joseph Eberth described a bacillus that he suspected was the cause of typhoid. Eberth is given credit for discovering the bacterium definitively by successfully isolating the same bacterium from 18 of 40 typhoid victims and failing to discover the bacterium present in any "control" victims of other diseases. In 1884, pathologist Georg Theodor August Gaffky (1850–1918) confirmed Eberth's findings. Gaffky isolated the same bacterium as Eberth from the spleen of a typhoid victim, and was able to grow the bacterium on solid media. The organism was given names such as Eberth's bacillus, Eberthella Typhi, and Gaffky-Eberth bacillus. Today, the bacillus that causes typhoid fever goes by the scientific name Salmonella enterica serovar Typhi.

Chlorination of water

Most developed countries had declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene. In 1893 attempts were made to chlorinate the water supply in Hamburg, Germany and in 1897 Maidstone, England, was the first town to have its entire water supply chlorinated. In 1905, following an outbreak of typhoid fever, the City of Lincoln, England, instituted permanent water chlorination. The first permanent disinfection of drinking water in the US was made in 1908 to the Jersey City, New Jersey, water supply. Credit for the decision to build the chlorination system has been given to John L. Leal. The chlorination facility was designed by George W. Fuller.

Outbreaks in traveling military groups led to the creation of the Lyster bag in 1915; a bag with a faucet which can be hung from a tree or pole, filled with water, and comes with a chlorination tablet to drop into the water. The Lyster bag was essential for the survival of American soldiers in the Vietnam War.

Direct transmission and carriers

Mary Mallon ("Typhoid Mary") in a hospital bed (foreground): She was forcibly quarantined as a carrier of typhoid fever in 1907 for three years and then again from 1915 until her death in 1938.

There were several occurrences of milk delivery men spreading typhoid fever throughout the communities they served. Although typhoid is not spread through milk itself, there were several examples of milk distributors in many locations watering their milk down with contaminated water, or cleaning the glass bottles the milk was placed in with contaminated water. Boston had two such cases around the turn of the 20th century. In 1899 there were 24 cases of typhoid traced to a single milkman, whose wife had died of typhoid fever a week before the outbreak. In 1908, J.J. Fallon, who was also a milkman, died of typhoid fever. Following his death and confirmation of the typhoid fever diagnosis, the city conducted an investigation of typhoid symptoms and cases along his route and found evidence of a significant outbreak. A month after the outbreak was first reported, the Boston Globe published a short statement declaring the outbreak over, stating "[a]t Jamaica Plain there is a slight increase, the total being 272 cases. Throughout the city there is a total of 348 cases." There was at least one death reported during this outbreak: Mrs. Sophia S. Engstrom, aged 46. Typhoid continued to ravage the Jamaica Plain neighborhood in particular throughout 1908, and several more people were reported dead due to typhoid fever, although these cases were not explicitly linked to the outbreak. The Jamaica Plain neighborhood at that time was home to many working-class and poor immigrants, mostly from Ireland.

The most notorious carrier of typhoid fever, but by no means the most destructive, was Mary Mallon, known as Typhoid Mary. Although other cases of human-to-human spread of typhoid were known at the time, the concept of an asymptomatic carrier, who was able to transmit disease, had only been hypothesized and not yet identified or proven. Mary Mallon became the first known example of an asymptomatic carrier of an infectious disease, making typhoid fever the first known disease being transmissible through asymptomatic hosts. The cases and deaths caused by Mallon were mainly upper-class families in New York City. At the time of Mallon's tenure as a personal cook for upper-class families, New York City reported 3,000 to 4,500 cases of typhoid fever annually. In the summer of 1906 two daughters of a wealthy family and maids working in their home became ill with typhoid fever. After investigating their home water sources and ruling out water contamination, the family hired civil engineer George Soper to conduct an investigation of the possible source of typhoid fever in the home. Soper described himself as an "epidemic fighter". His investigation ruled out many sources of food, and led him to question if the cook the family hired just prior to their household outbreak, Mallon, was the source. Since she had already left and begun employment elsewhere, he proceeded to track her down in order to obtain a stool sample. When he was able to finally meet Mallon in person he described her by saying "Mary had a good figure and might have been called athletic had she not been a little too heavy." In recounts of Soper's pursuit of Mallon, his only remorse appears to be that he was not given enough credit for his relentless pursuit and publication of her personal identifying information, stating that the media "rob[s] me of whatever credit belongs to the discovery of the first typhoid fever carrier to be found in America." Ultimately, 51 cases and 3 deaths were suspected to be caused by Mallon.

In 1924 the city of Portland, Oregon, experienced an outbreak of typhoid fever, consisting of 26 cases and 5 deaths, all deaths due to intestinal hemorrhage. All cases were concluded to be due to a single milk farm worker, who was shedding large amounts of the typhoid pathogen in his urine. Misidentification of the disease, due to inaccurate Widal test results, delayed identification of the carrier and proper treatment. Ultimately, it took four samplings of different secretions from all of the dairy workers in order to successfully identify the carrier. Upon discovery, the dairy worker was forcibly quarantined for seven weeks, and regular samples were taken, most of the time the stool samples yielding no typhoid and often the urine yielding the pathogen. The carrier was reported as being 72 years old and appearing in excellent health with no symptoms. Pharmaceutical treatment decreased the amount of bacteria secreted, however, the infection was never fully cleared from the urine, and the carrier was released "under orders never again to engage in the handling of foods for human consumption." At the time of release, the authors noted "for more than fifty years he has earned his living chiefly by milking cows and knows little of other forms of labor, it must be expected that the closest surveillance will be necessary to make certain that he does not again engage in this occupation."

Overall, in the early 20th century the medical profession began to identify carriers of the disease, and evidence of transmission independent of water contamination. In a 1933 American Medical Association publication, physicians' treatment of asymptomatic carriers is best summarized by the opening line "Carriers of typhoid bacilli are a menace". Within the same publication, the first official estimate of typhoid carriers is given: 2 to 5% of all typhoid patients, and distinguished between temporary carriers and chronic carriers. The authors further estimate that there are four to five chronic female carriers to every one male carrier, although offered no data to explain this assertion of a gender difference in the rate of typhoid carriers. As far as treatment, the authors suggest: "When recognized, carriers must be instructed as to the disposal of excreta as well as to the importance of personal cleanliness. They should be forbidden to handle food or drink intended for others, and their movements and whereabouts must be reported to the public health officers".

New Typhoid carrier cases reported in L.A. County between 2006 and 2016

Today, typhoid carriers exist all over the world, but the highest incidence of asymptomatic infection is likely to occur in South/Southeast Asian and Sub-Saharan countries. The Los Angeles County department of public health tracks typhoid carriers and reports the number of carriers identified within the county yearly; between 2006 and 2016 0-4 new cases of typhoid carriers were identified per year. Cases of typhoid fever must be reported within one working day from identification. As of 2018, chronic typhoid carriers must sign a "Carrier Agreement" and are required to test for typhoid shedding twice yearly, ideally every 6 months. Carriers may be released from their agreements upon fulfilling "release" requirements, based on completion of a personalized treatment plan designed with medical professionals. Fecal or gallbladder carrier release requirements: 6 consecutive negative feces and urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy. Urinary or kidney carrier release requirements: 6 consecutive negative urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy. As of 2016 the male:female ratio of carriers in Los Angeles county was 3:1.

Due to the nature of asymptomatic cases, many questions remain about how individuals are able to tolerate infection for long periods of time, how to identify such cases, and efficient options for treatment. Researchers are currently working to understand asymptomatic infection with Salmonella species by studying infections in laboratory animals, which will ultimately lead to improved prevention and treatment options for typhoid carriers. In 2002, John Gunn described the ability of Salmonella sp. to form biofilms on gallstones in mice, providing a model for studying carriage in the gallbladder. Denise Monack and Stanley Falkow described a mouse model of asymptomatic intestinal and systemic infection in 2004, and Monack went on to demonstrate that a sub-population of superspreaders are responsible for the majority of transmission to new hosts, following the 80/20 rule of disease transmission, and that the intestinal microbiota likely plays a role in transmission. Monack's mouse model allows long-term carriage of salmonella in mesenteric lymph nodes, spleen and liver.

Vaccine development

Almroth Edward Wright developed the first effective typhoid vaccine.

British bacteriologist Almroth Edward Wright first developed an effective typhoid vaccine at the Army Medical School in Netley, Hampshire. It was introduced in 1896 and used successfully by the British during the Second Boer War in South Africa. At that time, typhoid often killed more soldiers at war than were lost due to enemy combat. Wright further developed his vaccine at a newly opened research department at St Mary's Hospital Medical School in London from 1902, where he established a method for measuring protective substances (opsonin) in human blood. Wright's version of the typhoid vaccine was produced by growing the bacterium at body temperature in broth, then heating the bacteria to 60 °C to "heat inactivate" the pathogen, killing it, while keeping the surface antigens intact. The heat-killed bacteria was then injected into a patient. To show evidence of the vaccine's efficacy, Wright then collected serum samples from patients several weeks post-vaccination, and tested their serum's ability to agglutinate live typhoid bacteria. A "positive" result was represented by clumping of bacteria, indicating that the body was producing anti-serum (now called antibodies) against the pathogen.

Citing the example of the Second Boer War, during which many soldiers died from easily preventable diseases, Wright convinced the British Army that 10 million vaccine doses should be produced for the troops being sent to the Western Front, thereby saving up to half a million lives during World War I. The British Army was the only combatant at the outbreak of the war to have its troops fully immunized against the bacterium. For the first time, their casualties due to combat exceeded those from disease.

In 1909, Frederick F. Russell, a U.S. Army physician, adopted Wright's typhoid vaccine for use with the Army, and two years later, his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military. Typhoid vaccination for members of the American military became mandatory in 1911. Before the vaccine, the rate of typhoid fever in the military was 14,000 or greater per 100,000 soldiers. By World War I, the rate of typhoid in American soldiers was 37 per 100,000.

During the second world war, the United States army authorized the use of a trivalent vaccine – containing heat-inactivated Typhoid, Paratyphi A and Paratyphi B pathogens.

In 1934, discovery of the Vi capsular antigen by Arthur Felix and Miss S. R. Margaret Pitt enabled development of the safer Vi Antigen vaccine – which is widely in use today. Arthur Felix and Margaret Pitt also isolated the strain Ty2, which became the parent strain of Ty21a, the strain used as a live-attenuated vaccine for typhoid fever today.

Antibiotics and resistance

Chloramphenicol was isolated from Streptomyces by David Gotlieb during the 1940s. In 1948 American army doctors tested its efficacy in treating typhoid patients in Kuala Lumpur, Malaysia. Individuals who received a full course of treatment cleared the infection, whereas patients given a lower dose had a relapse. Asymptomatic carriers continued to shed bacilli despite chloramphenicol treatment - only ill patients were improved with chloramphenicol. Resistance to chloramphenicol became frequent in Southeast Asia by the 1950s, and today chloramphenicol is only used as a last resort due to the high prevalence of resistance.

Terminology

The disease has been referred to by various names, often associated with symptoms, such as gastric fever, enteric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever, pythogenic fever, drain fever and low fever.

Genocide

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Genocide

Genocide is the intentional destruction of a people in whole or in part. Raphael Lemkin coined the term in 1944, combining the Greek word γένος (genos, "race, people") with the Latin suffix -caedo ("act of killing").

In 1948, the United Nations Genocide Convention defined genocide as any of five "acts committed with intent to destroy, in whole or in part, a national, ethnical, racial or religious group." These five acts were: killing members of the group, causing them serious bodily or mental harm, imposing living conditions intended to destroy the group, preventing births, and forcibly transferring children out of the group. Victims are targeted because of their real or perceived membership of a group, not randomly.

The Political Instability Task Force estimated that 43 genocides occurred between 1956 and 2016, resulting in about 50 million deaths. The UNHCR estimated that a further 50 million had been displaced by such episodes of violence up to 2008. Genocide, especially large-scale genocide, is widely considered to signify the epitome of human evil. As a label, it is contentious because it is moralizing, and has been used as a type of moral category since the late 1990s.

Etymology

Aftermath of the 1941 Odessa massacre, in which Jewish deportees were killed outside Brizula (now Podilsk) during the Holocaust

 

Members of the Sonderkommando burn corpses of Jews in pits at Auschwitz II-Birkenau, an extermination camp.

Before the term genocide was coined, there were various ways of describing such events. Some languages already had words for such killings, including German (Völkermord, lit. 'murder of a people') and Polish (ludobójstwo, lit. 'killing of a people or nation'). In 1941, when describing the "methodical, merciless butchery" of "scores of thousands" of Russians by Nazi troops during the German invasion of the Soviet Union, Winston Churchill spoke of "a crime without a name". In 1944, Raphael Lemkin coined the term genocide as a hybrid combination of the Ancient Greek word γένος (génos) 'race, people' with the Latin caedere, 'to kill'; his book Axis Rule in Occupied Europe (1944) describes the implementation of Nazi policies in occupied Europe and mentions earlier mass killings. After reading about the 1921 assassination of Talat Pasha, the main architect of the Armenian genocide, by Armenian Soghomon Tehlirian, Lemkin asked his professor why there was no law under which Talat could be charged. He later explained that "as a lawyer, I thought that a crime should not be punished by the victims, but should be punished by a court."

Lemkin defined genocide as follows:

New conceptions require new terms. By "genocide" we mean the destruction of a nation or of an ethnic group. This new word, coined by the author to denote an old practice in its modern development, is made from the ancient Greek word genos (race, tribe) and the Latin cide (killing), thus corresponding in its formation to such words as tyrannicide, homicide, infanticide, etc. Generally speaking, genocide does not necessarily mean the immediate destruction of a nation, except when accomplished by mass killings of all members of a nation. It is intended rather to signify a coordinated plan of different actions aiming at the destruction of essential foundations of the life of national groups, with the aim of annihilating the groups themselves. The objectives of such a plan would be disintegration of the political and social institutions, of culture, language, national feelings, religion, and the economic existence of national groups, and the destruction of the personal security, liberty, health, dignity, and even the lives of the individuals belonging to such groups. Genocide is directed against the national group as an entity, and the actions involved are directed against individuals, not in their individual capacity, but as members of the national group.

The preamble to the 1948 Genocide Convention (CPPCG) notes that instances of genocide have taken place throughout history; it was not until Lemkin coined the term and the prosecution of perpetrators of the Holocaust at the Nuremberg Trials that the United Nations defined the crime of genocide under international law in the Genocide Convention. It was several years before the term was widely adopted by the international community. When the Nuremberg trials revealed the inadequacy of phrases like "Germanization", "crimes against humanity" and "mass murder", scholars of international law reached agreement that Lemkin's work provided a conceptual framework for Nazi crimes. A 1946 headline in The New York Times announced that "Genocide Is the New Name for the Crime Fastened on the Nazi Leaders"; the word was used in indictments at the Nuremberg trials, held from 1945, but solely as a descriptive term, not yet as a formal legal term. The so-called Polish Genocide Trials of Arthur Greiser and Amon Leopold Goth in 1946 were the first trials in which judgments included the term.

Prohibited acts

The Genocide Convention establishes five prohibited acts that, when committed with the requisite intent, amount to genocide. Although massacre-style killings are the most commonly identified and punished as genocide, the range of violence that is contemplated by the law is significantly broader.

Killing members of the group

While mass killing is not necessary for genocide to have been committed, it has been present in almost all recognized genocides. A near-uniform pattern has emerged throughout history in which men and adolescent boys are singled out for murder in the early stages, such as in the genocide of the Yazidis by Daesh, the Ottoman Turks' attack on the Armenians, and the Burmese security forces' attacks on the Rohingya. Men and boys are typically subject to "fast" killings, such as by gunshot. Women and girls are more likely to die slower deaths by slashing, burning, or as a result of sexual violence. The jurisprudence of the International Criminal Tribunal for Rwanda (ICTR), among others, shows that both the initial executions and those that quickly follow other acts of extreme violence, such as rape and torture, are recognized as falling under the first prohibited act.

A less settled discussion is whether deaths that are further removed from the initial acts of violence can be addressed under this provision of the Genocide Convention. Legal scholars have posited, for example, that deaths resulting from other genocidal acts including causing serious bodily or mental harm or the successful deliberate infliction of conditions of life calculated to bring about physical destruction should be considered genocidal killings.

Causing serious bodily or mental harm to members of the group Article II(b)

This second prohibited act can encompass a wide range of non-fatal genocidal acts. The ICTR and International Criminal Tribunal for the former Yugoslavia (ICTY) have held that rape and sexual violence may constitute the second prohibited act of genocide by causing both physical and mental harm. In its landmark Akayesu decision, the ICTR held that rapes and sexual violence resulted in "physical and psychological destruction". Sexual violence is a hallmark of genocidal violence, with most genocidal campaigns explicitly or implicitly sanctioning it. It is estimated that 250,000 to 500,000 women were raped in the three months of the Rwandan genocide, many of whom were subjected to multiple rapes or gang rape. In Darfur, a systemic campaign of rape and often sexual mutilation was carried out and in Burma public mass rapes and gang rapes were inflicted on the Rohingya by Burmese security forces. Sexual slavery was documented in the Armenian genocide by the Ottoman Turks and Daesh's genocide of the Yazidi.

Torture and other cruel, inhuman, or degrading treatment or punishment, when committed with the requisite intent, are also genocide by causing serious bodily or mental harm to members of the group. The ICTY found that both experiencing a failed execution and watching the murder of one's family members may constitute torture. The Syrian Commission of Inquiry (COI) also found that enslavement, removal of one's children into indoctrination or sexual slavery, and acts of physical and sexual violence rise to the level of torture, as well. While it was subject to some debate, the ICTY and, later, the Syrian COI held that under some circumstances deportation and forcible transfer may also cause serious bodily or mental harm.

Deliberately inflicting on the group conditions of life calculated to bring about its physical destruction

The U.S. federal government promoted bison hunting for various reasons, including as a way of destroying the means of survival of Plains Indians to pressure them to remain on Indian reservations.

The third prohibited act is distinguished from the genocidal act of killing because the deaths are not immediate (or may not even come to pass), but rather create circumstances that do not support prolonged life. Due to the longer period of time before the actual destruction would be achieved, the ICTR held that courts must consider the duration of time the conditions are imposed as an element of the act. In the 19th century the United States federal government supported the extermination of bison, which Native Americans in the Great Plains relied on as a source of food. This was done for various reasons, primarily to pressure them onto reservations during times of conflict. Some genocide experts describe this as an example of genocide that involves removing the means of survival.

The ICTR provided guidance into what constitutes a violation of the third act. In Akayesu, it identified "subjecting a group of people to a subsistence diet, systematic expulsion from homes and the reduction of essential medical services below minimum requirement" as rising to genocide. In Kayishema and Ruzindana, it extended the list to include: "lack of proper housing, clothing, hygiene and medical care or excessive work or physical exertion" among the conditions. It further noted that, in addition to deprivation of necessary resources, rape could also fit within this prohibited act.

Imposing measures intended to prevent births within the group

See also: Compulsory sterilization

The fourth prohibited act is aimed at preventing the protected group from regenerating through reproduction. It encompasses acts affecting reproduction and intimate relationships, such as involuntary sterilization, forced abortion, the prohibition of marriage, and long-term separation of men and women intended to prevent procreation. Rape has been found to violate the fourth prohibited act on two bases: where the rape was committed with the intent to impregnate a woman and thereby force her to carry a child of another group (in societies where group identity is determined by patrilineal identity) and where the person raped subsequently refuses to procreate as a result of the trauma. Accordingly, it can take into account both physical and mental measures imposed by the perpetrators.

Forcibly transferring children of the group to another group

See also: Forced assimilation

The final prohibited act is the only prohibited act that does not lead to physical or biological destruction, but rather to destruction of the group as a cultural and social unit. It occurs when children of the protected group are transferred to the perpetrator group. Boys are typically taken into the group by changing their names to those common of the perpetrator group, converting their religion, and using them for labor or as soldiers. Girls who are transferred are not generally converted to the perpetrator group, but instead treated as chattel, as played out in both the Yazidi and Armenian genocides.

Crime

Pre-criminalization view

Before genocide was made a crime against national law, it was considered a sovereign right. When Lemkin asked about a way to punish the perpetrators of the Armenian genocide, a law professor told him: "Consider the case of a farmer who owns a flock of chickens. He kills them and this is his business. If you interfere, you are trespassing." As late as 1959, many world leaders still "believed states had a right to commit genocide against people within their borders", according to political scientist Douglas Irvin-Erickson.

International law

Human skulls at the Murambi Genocide Memorial Centre in Rwanda

 

Armenian genocide victims

After the Holocaust, which had been perpetrated by Nazi Germany prior to and during World War II, Lemkin successfully campaigned for the universal acceptance of international laws defining and forbidding genocides. In 1946, the first session of the United Nations General Assembly adopted a resolution that affirmed genocide was a crime under international law and enumerated examples of such events (but did not provide a full legal definition of the crime). In 1948, the UN General Assembly adopted the Convention on the Prevention and Punishment of the Crime of Genocide (CPPCG) which defined the crime of genocide for the first time.

Genocide is a denial of the right of existence of entire human groups, as homicide is the denial of the right to live of individual human beings; such denial of the right of existence shocks the conscience of mankind, results in great losses to humanity in the form of cultural and other contributions represented by these human groups, and is contrary to moral law and the spirit and aims of the United Nations. Many instances of such crimes of genocide have occurred when racial, religious, political and other groups have been destroyed, entirely or in part.

— UN Resolution 96(1), 11 December 1946

The CPPCG was adopted by the UN General Assembly on 9 December 1948 and came into effect on 12 January 1951 (Resolution 260 (III)). It contains an internationally recognized definition of genocide which has been incorporated into the national criminal legislation of many countries and was also adopted by the Rome Statute of the International Criminal Court, which established the International Criminal Court (ICC). Article II of the Convention defines genocide as:

... any of the following acts committed with intent to destroy, in whole or in part, a national, ethnical, racial or religious group, as such:

• (a) Killing members of the group;
• (b) Causing serious bodily or mental harm to members of the group;
• (c) Deliberately inflicting on the group conditions of life calculated to bring about its physical destruction in whole or in part;
• (d) Imposing measures intended to prevent births within the group;
• (e) Forcibly transferring children of the group to another group.

Incitement to genocide is recognized as a separate crime under international law and an inchoate crime which does not require genocide to have taken place to be prosecutable.

The first draft of the convention included political killings; these provisions were removed in a political and diplomatic compromise following objections from many diverse countries, and originally promoted by the World Jewish Congress and Raphael Lemkin's conception, with some scholars popularly emphasizing in literature the role of the Soviet Union, a permanent United Nations Security Council member. The Soviets argued that the convention's definition should follow the etymology of the term, and Joseph Stalin in particular may have feared greater international scrutiny of the country's political killings, such as the Great Purge. Lemkin, who coined genocide, approached the Soviet delegation as the resolution vote came close to reassure the Soviets that there was no conspiracy against them; none in the Soviet-led bloc opposed the resolution, which passed unanimously in December 1946. Other nations, including the United States, feared that including political groups in the definition would invite international intervention in domestic politics.

By 1951, Lemkin was saying that the Soviet Union was the only state that could be indicted for genocide, his concept of genocide, as outlined in Axis Rule in Occupied Europe, covering Stalinist deportations as genocide by default, and differing in many ways from the adopted Genocide Convention. From a 21st-century perspective, it was such a broad coverage that it would include any grossly human rights violation as genocide, and that many events deemed by Lemkin genocidal did not amount to genocide. As the Cold War began, this change was the result of Lemkin's turn to anti-communism in an attempt to convince the United States to ratify the Genocide Convention.

Intent

Under international law, genocide has two mental (mens rea) elements: the general mental element and the element of specific intent (dolus specialis). The general element refers to whether the prohibited acts were committed with intent, knowledge, recklessness, or negligence. For most serious international crimes, including genocide, the requirement is that the perpetrator act with intent. The Rome Statute defines intent as meaning to engage in the conduct and, in relation to consequences, as meaning to cause that consequence or being "aware that it will occur in the ordinary course of events".

The specific intent element defines the purpose of committing the acts: "to destroy in whole or in part, a national, ethnical, racial or religious group, as such". The specific intent is a core factor distinguishing genocide from other international crimes, such as war crimes or crimes against humanity.

"Intent to destroy"

Main article: Genocidal intent

In 2007, the European Court of Human Rights (ECHR) noted in its judgement on Jorgic v. Germany case that, in 1992, the majority of legal scholars took the narrow view that "intent to destroy" in the CPPCG meant the intended physical-biological destruction of the protected group, and that this was still the majority opinion. But the ECHR also noted that a minority took a broader view, and did not consider biological-physical destruction to be necessary, as the intent to destroy a national, racial, religious or ethnic group was enough to qualify as genocide.

In the same judgement, the ECHR reviewed the judgements of several international and municipal courts. It noted that the International Criminal Tribunal for the former Yugoslavia and the International Court of Justice had agreed with the narrow interpretation (that biological-physical destruction was necessary for an act to qualify as genocide). The ECHR also noted that at the time of its judgement, apart from courts in Germany (which had taken a broad view), that there had been few cases of genocide under other Convention states' municipal laws, and that "There are no reported cases in which the courts of these States have defined the type of group destruction the perpetrator must have intended in order to be found guilty of genocide."

In the case of "Onesphore Rwabukombe", the German Federal Court of Justice adhered to its previous judgement, and did not follow the narrow interpretation of the ICTY and the ICJ.

"In whole or in part"

The phrase "in whole or in part" has been subject to much discussion by scholars of international humanitarian law. In the Ruhashyankiko report of the United Nations it was once argued that the killing of only a single individual could be genocide if the intent to destroy the wider group was found in the murder, yet official court rulings have since contradicted this. The International Criminal Tribunal for the Former Yugoslavia found in Prosecutor v. Radislav Krstic – Trial Chamber I – Judgment – IT-98-33 (2001) ICTY8 (2 August 2001) that Genocide had been committed. In Prosecutor v. Radislav Krstic – Appeals Chamber – Judgment – IT-98-33 (2004) ICTY 7 (19 April 2004) paragraphs 8, 9, 10, and 11 addressed the issue of in part and found that "the part must be a substantial part of that group. The aim of the Genocide Convention is to prevent the intentional destruction of entire human groups, and the part targeted must be significant enough to have an impact on the group as a whole." The Appeals Chamber goes into details of other cases and the opinions of respected commentators on the Genocide Convention to explain how they came to this conclusion.

The judges continue in paragraph 12, "The determination of when the targeted part is substantial enough to meet this requirement may involve a number of considerations. The numeric size of the targeted part of the group is the necessary and important starting point, though not in all cases the ending point of the inquiry. The number of individuals targeted should be evaluated not only in absolute terms but also in relation to the overall size of the entire group. In addition to the numeric size of the targeted portion, its prominence within the group can be a useful consideration. If a specific part of the group is emblematic of the overall group or is essential to its survival, that may support a finding that the part qualifies as substantial within the meaning of Article 4 [of the Tribunal's Statute]."

In paragraph 13 the judges raise the issue of the perpetrators' access to the victims: "The historical examples of genocide also suggest that the area of the perpetrators' activity and control, as well as the possible extent of their reach, should be considered. ... The intent to destroy formed by a perpetrator of genocide will always be limited by the opportunity presented to him. While this factor alone will not indicate whether the targeted group is substantial, it can—in combination with other factors—inform the analysis."

"A national, ethnic, racial or religious group"

The drafters of the CPPCG chose not to include political or social groups among the protected groups. Instead, they opted to focus on "stable" identities, attributes that are historically understood as being born into and unable or unlikely to change over time. This definition conflicts with modern conceptions of race as a social construct rather than innate fact and the practice of changing religion, etc.

International criminal courts have typically applied a mix of objective and subjective markers for determining whether or not a targeted population is a distinct group. Differences in language, physical appearance, religion, and cultural practices are objective criteria that may show that the groups are distinct. However, in circumstances such as the Rwandan genocide, Hutus and Tutsis were often physically indistinguishable.

In such a situation where a definitive answer based on objective markers is not clear, courts have turned to the subjective standard that "if a victim was perceived by a perpetrator as belonging to a protected group, the victim could be considered by the Chamber as a member of the protected group". Stigmatization of the group by the perpetrators through legal measures, such as withholding citizenship, requiring the group to be identified, or isolating them from the whole could show that the perpetrators viewed the victims as a protected group.

Convention on the Prevention and Punishment of the Crime of Genocide

The convention came into force as international law on 12 January 1951 after the minimum 20 countries became parties. At that time however, only two of the five permanent members of the UN Security Council were parties to the treaty: France and the Republic of China. The Soviet Union ratified in 1954, the United Kingdom in 1970, the People's Republic of China in 1983 (having replaced the Taiwan-based Republic of China on the UNSC in 1971), and the United States in 1988.

William Schabas has suggested that a permanent body as recommended by the Whitaker Report to monitor the implementation of the Genocide Convention, and require states to issue reports on their compliance with the convention (such as were incorporated into the United Nations Optional Protocol to the Convention against Torture), would make the convention more effective.

UN Security Council Resolution 1674

UN Security Council Resolution 1674, adopted by the United Nations Security Council on 28 April 2006, "reaffirms the provisions of paragraphs 138 and 139 of the 2005 World Summit Outcome Document regarding the responsibility to protect populations from genocide, war crimes, ethnic cleansing and crimes against humanity". The resolution committed the council to action to protect civilians in armed conflict.

In 2008 the UN Security Council adopted resolution 1820, which noted that "rape and other forms of sexual violence can constitute war crimes, crimes against humanity or a constitutive act with respect to genocide".

Municipal law

Main article: Genocide under municipal laws

Since the Convention came into effect in January 1951 about 80 United Nations member states have passed legislation that incorporates the provisions of CPPCG into their municipal law.

Other definitions of genocide

See also: Genocide definitions

Writing in 1998, Kurt Jonassohn and Karin Björnson stated that the CPPCG was a legal instrument resulting from a diplomatic compromise. As such the wording of the treaty is not intended to be a definition suitable as a research tool, and although it is used for this purpose, as it has international legal credibility that others lack, other genocide definitions have also been proposed. They go on to say that none of these alternative definitions have gained widespread support, they postulate that the major reason why no generally accepted genocide definition has emerged is because academics have adjusted their focus to emphasise different periods and have found it expedient to use slightly different definitions. For example, Frank Chalk and Kurt Jonassohn studied all human history, while Leo Kuper and Rudolph Rummel concentrated on the 20th century, and Helen Fein, Barbara Harff, and Ted Gurr looked at post-World War II events.

Yehuda Bauer, has argued that the present definition is problematic, contending that many of what are usually called genocides were not racially motivated. Bauer gave the Rwandan Genocide, where, Bauer argued, both the perpetrators and victims were of the same ethnicity, as an example. He argued that, because of this discrepancy, "clearly, the existing definition of genocide is inadequate and needs to be altered."

Political and social groups

The exclusion of social and political groups as targets of genocide in the CPPCG legal definition has been criticized by some historians and sociologists, for example, M. Hassan Kakar in his book The Soviet Invasion and the Afghan Response, 1979–1982 argues that the international definition of genocide is too restricted, and that it should include political groups or any group so defined by the perpetrator and quotes Chalk and Jonassohn: "Genocide is a form of one-sided mass killing in which a state or other authority intends to destroy a group, as that group and membership in it are defined by the perpetrator." In turn some states such as Ethiopia, France, and Spain include political groups as legitimate genocide victims in their anti-genocide laws.

Harff and Gurr defined genocide as "the promotion and execution of policies by a state or its agents which result in the deaths of a substantial portion of a group ... [when] the victimized groups are defined primarily in terms of their communal characteristics, i.e., ethnicity, religion or nationality". Harff and Gurr also differentiate between genocides and politicides by the characteristics by which members of a group are identified by the state. In genocides, the victimized groups are defined primarily in terms of their communal characteristics, i.e., ethnicity, religion or nationality. In politicides the victim groups are defined primarily in terms of their hierarchical position or political opposition to the regime and dominant groups. Daniel D. Polsby and Don B. Kates, Jr. state that "we follow Harff's distinction between genocides and 'pogroms', which she describes as 'short-lived outbursts by mobs, which, although often condoned by authorities, rarely persist'. If the violence persists for long enough, however, Harff argues, the distinction between condonation and complicity collapses."

According to Rummel, genocide has three different meanings. The ordinary meaning is murder by the government of people due to their national, ethnic, racial, or religious group membership. The legal meaning of genocide refers to the international treaty, the Convention on the Prevention and Punishment of the Crime of Genocide (CPPCG). This also includes non-killings that in the end eliminate the group, such as preventing births or forcibly transferring children out of the group to another group.

Highlighting the potential for state and non-state actors to commit genocide in the 21st century, for example, in failed states or as non-state actors acquiring weapons of mass destruction, Adrian Gallagher defined genocide as 'When a source of collective power (usually a state) intentionally uses its power base to implement a process of destruction in order to destroy a group (as defined by the perpetrator), in whole or in substantial part, dependent upon relative group size'. The definition upholds the centrality of intent, the multidimensional understanding of destroying, broadens the definition of group identity beyond that of the 1948 definition yet argues that a substantial part of a group has to be destroyed before it can be classified as genocide.

Other proposed definitions of genocide include social groups defined by gender, sexual orientation, or gender identity.

Democide

Democide, a term devised by American political scientist Rudolph Rummel, describes "the intentional killing of an unarmed or disarmed person by government agents acting in their authoritative capacity and pursuant to government policy or high command." This definition covers any murder of any number of persons by any government, including government mandated forced labor, concentration camps, extrajudicial summary killings, civil wars, and mass deaths due to government neglect such as government induced famines like Holodomor. Rummel estimates that in the 20th century, democide resulted in over 262 million deaths.

Holocaust historian Yehuda Bauer agreed with Rummel that democide was a more appropriate term in more cases to describe mass atrocities than genocide due to the more inclusive definition of democide versus genocide.

Transgender genocide

Main article: Transgender genocide

In 2013 some international trans activists introduced the term ‘transcide’ to describe the elevated level of killings of trans people globally. A coalition of NGOs from South America and Europe started the "Stop Trans Genocide" campaign. The term "trancide" follows an earlier term, gendercide. Legal scholars have argued that the definition of genocide should be expanded to cover transgender people, because they are victims of institutional discrimination, persecution, and violence. Brian Kritz argued that existing law should be extended to protect transgender people. Similar arguments have been made regarding extending the legal definition of "crimes against humanity." Aside from legal studies, transgender genocide has been examined by scholars of queer studies, hate studies, and other fields.

International prosecution

By ad hoc tribunals

Nuon Chea, the Khmer Rouge's chief ideologist, before the Cambodian Genocide Tribunal on 5 December 2011

All signatories to the CPPCG are required to prevent and punish acts of genocide, both in peace and wartime, though some barriers make this enforcement difficult. In particular, some of the signatories—namely, Bahrain, Bangladesh, India, Malaysia, the Philippines, Singapore, the United States, Vietnam, Yemen, and former Yugoslavia—signed with the proviso that no claim of genocide could be brought against them at the International Court of Justice without their consent. Despite official protests from other signatories (notably Cyprus and Norway) on the ethics and legal standing of these reservations, the immunity from prosecution they grant has been invoked from time to time, as when the United States refused to allow a charge of genocide brought against it by former Yugoslavia following the 1999 Kosovo War.

It is commonly accepted that, at least since World War II, genocide has been illegal under customary international law as a peremptory norm, as well as under conventional international law. Acts of genocide are generally difficult to establish for prosecution because a chain of accountability must be established. International criminal courts and tribunals function primarily because the states involved are incapable or unwilling to prosecute crimes of this magnitude themselves.

Nuremberg Tribunal (1945–1946)

Main article: Nuremberg trials

 

The Nazi leaders at the Palace of Justice, Nuremberg

The Nazi leaders who were prosecuted shortly after World War II for taking part in the Holocaust, and other mass murders, were charged under existing international laws, such as crimes against humanity, as the crime of "genocide' was not formally defined until the 1948 Convention on the Prevention and Punishment of the Crime of Genocide (CPPCG). Nevertheless, the recently coined term appeared in the indictment of the Nazi leaders, Count 3, which stated that those charged had "conducted deliberate and systematic genocide—namely, the extermination of racial and national groups—against the civilian populations of certain occupied territories in order to destroy particular races and classes of people, and national, racial or religious groups, particularly Jews, Poles, Gypsies and others."

International Criminal Tribunal for the Former Yugoslavia (1993–2017)

See also: Bosnian genocide and List of Bosnian genocide prosecutions

 

The cemetery at the Srebrenica-Potočari Memorial and Cemetery to Genocide Victims

The term Bosnian genocide is used to refer either to the killings committed by Serb forces in Srebrenica in 1995, or to ethnic cleansing that took place elsewhere during the 1992–1995 Bosnian War.

In 2001, the International Criminal Tribunal for the Former Yugoslavia (ICTY) judged that the 1995 Srebrenica massacre was an act of genocide. On 26 February 2007, the International Court of Justice (ICJ), in the Bosnian Genocide Case upheld the ICTY's earlier finding that the massacre in Srebrenica and Zepa constituted genocide, but found that the Serbian government had not participated in a wider genocide on the territory of Bosnia and Herzegovina during the war, as the Bosnian government had claimed.

On 12 July 2007, European Court of Human Rights when dismissing the appeal by Nikola Jorgić against his conviction for genocide by a German court (Jorgic v. Germany) noted that the German courts wider interpretation of genocide has since been rejected by international courts considering similar cases. The ECHR also noted that in the 21st century "Amongst scholars, the majority have taken the view that ethnic cleansing, in the way in which it was carried out by the Serb forces in Bosnia and Herzegovina in order to expel Muslims and Croats from their homes, did not constitute genocide. However, there are also a considerable number of scholars who have suggested that these acts did amount to genocide, and the ICTY has found in the Momcilo Krajisnik case that the actus reus of genocide was met in Prijedor "With regard to the charge of genocide, the Chamber found that in spite of evidence of acts perpetrated in the municipalities which constituted the actus reus of genocide".

About 30 people have been indicted for participating in genocide or complicity in genocide during the early 1990s in Bosnia. To date, after several plea bargains and some convictions that were successfully challenged on appeal two men, Vujadin Popović and Ljubiša Beara, have been found guilty of committing genocide, Zdravko Tolimir has been found guilty of committing genocide and conspiracy to commit genocide, and two others, Radislav Krstić and Drago Nikolić, have been found guilty of aiding and abetting genocide. Three others have been found guilty of participating in genocides in Bosnia by German courts, one of whom Nikola Jorgić lost an appeal against his conviction in the European Court of Human Rights. A further eight men, former members of the Bosnian Serb security forces were found guilty of genocide by the State Court of Bosnia and Herzegovina (See List of Bosnian genocide prosecutions).

Slobodan Milošević, as the former President of Serbia and of Yugoslavia, was the most senior political figure to stand trial at the ICTY. He died on 11 March 2006 during his trial where he was accused of genocide or complicity in genocide in territories within Bosnia and Herzegovina, so no verdict was returned. In 1995, the ICTY issued a warrant for the arrest of Bosnian Serbs Radovan Karadžić and Ratko Mladić on several charges including genocide. On 21 July 2008, Karadžić was arrested in Belgrade, and later tried in The Hague accused of genocide among other crimes. On 24 March 2016, Karadžić was found guilty of genocide in Srebrenica, war crimes and crimes against humanity, 10 of the 11 charges in total, and sentenced to 40 years' imprisonment. Mladić was arrested on 26 May 2011 in Lazarevo, Serbia, and was tried in The Hague. The verdict, delivered on 22 November 2017 found Mladić guilty of 10 of the 11 charges, including genocide and he was sentenced to life imprisonment.

International Criminal Tribunal for Rwanda (1994–present)

See also: Rwandan genocide

 

Photographs of Rwandan genocide victims displayed at the Genocide Memorial Center in Kigali

The International Criminal Tribunal for Rwanda (ICTR) is a court under the auspices of the United Nations for the prosecution of offenses committed in Rwanda during the genocide which occurred there during April 1994, commencing on 6 April. The ICTR was created on 8 November 1994 by the Security Council of the United Nations in order to judge those people responsible for the acts of genocide and other serious violations of the international law performed in the territory of Rwanda, or by Rwandan citizens in nearby states, between 1 January and 31 December 1994.

So far, the ICTR has finished nineteen trials and convicted twenty-seven accused persons. On 14 December 2009, two more men were accused and convicted for their crimes. Another twenty-five persons are still on trial. Twenty-one are awaiting trial in detention, two more added on 14 December 2009. Ten are still at large. The first trial, of Jean-Paul Akayesu, began in 1997. Akayesu was the first person ever to be convicted of the crime of genocide. In October 1998, Akayesu was sentenced to life imprisonment. Jean Kambanda, interim Prime Minister, pleaded guilty.

Trials for deeds committed during the Rwandan genocide have also occurred in national courts, including Désiré Munyaneza, who in 2009 became the first man to be arrested and convicted in Canada on charges of war crimes and crimes against humanity, and Yvonne Ntacyobatabara Basebya, who in 2013 became the first Dutch citizen to be convicted for incitement to genocide.

Extraordinary Chambers in the Courts of Cambodia (from 2003)

Main articles: Khmer Rouge Tribunal and Cambodian genocide

 

Rooms of the Tuol Sleng Genocide Museum contain thousands of photos taken by the Khmer Rouge of their victims.

 

Skulls in the Choeung Ek

The Khmer Rouge, led by Pol Pot, Kang Kek Iew, Ta Mok and other leaders, organized the mass killing of ideologically suspect groups. The total number of victims is estimated at 1.7 million Cambodians between 1975 and 1979, including deaths from slave labour.

On 6 June 2003 the Cambodian government and the United Nations reached an agreement to set up the Extraordinary Chambers in the Courts of Cambodia (ECCC) which would focus exclusively on crimes committed by the most senior Khmer Rouge officials during the period of Khmer Rouge rule of 1975–1979. The judges were sworn in early July 2006.

The genocide charges related to killings of Cambodia's Vietnamese and Cham minorities, tens of thousand of whom are estimated to have been killed.

The investigating judges were presented with the names of four suspects charged with genocide on 18 July 2007.

• Nuon Chea, a former prime minister, was indicted on charges of genocide, war crimes, crimes against humanity on 15 September 2010. His trial started on 27 June 2011 and ended on 7 August 2014, with a life sentence imposed for crimes against humanity.
• Khieu Samphan, a former head of state, was indicted on charges of genocide, war crimes, crimes against humanity on 15 September 2010. His trial began on 27 June 2011. and also ended on 7 August 2014, with a life sentence imposed for crimes against humanity.
• Ieng Sary, a former foreign minister, was indicted on charges of genocide, war crimes, crimes against humanity on 15 September 2010. His trial started on 27 June 2011, and ended with his death on 14 March 2013. He was never convicted.
• Ieng Thirith, a former minister for social affairs and wife of Ieng Sary, was indicted on charges of genocide, war crimes, crimes against humanity on 15 September 2010. Proceedings against her were suspended pending a health evaluation. In September 2012, she was released from prison due to advanced Alzheimer's disease; she died on 22 August 2015 at the age of 83 from complications of the disease.

By the International Criminal Court

Since 2002, the International Criminal Court can exercise its jurisdiction if national courts are unwilling or unable to investigate or prosecute genocide, thus being a "court of last resort," leaving the primary responsibility to exercise jurisdiction over alleged criminals to individual states. Due to the United States concerns over the ICC, the United States prefers to continue to use specially convened international tribunals for such investigations and potential prosecutions.

Darfur, Sudan

Main article: War in Darfur

A mother with her sick baby at Abu Shouk IDP camp in North Darfur

There has been much debate over categorizing the situation in Darfur as genocide. The ongoing conflict in Darfur, Sudan, which started in 2003, was declared a "genocide" by United States Secretary of State Colin Powell on 9 September 2004 in testimony before the Senate Foreign Relations Committee. Since that time however, no other permanent member of the UN Security Council has done so. In fact, in January 2005, an International Commission of Inquiry on Darfur, authorized by UN Security Council Resolution 1564 of 2004, issued a report to the Secretary-General stating that "the Government of Sudan has not pursued a policy of genocide." Nevertheless, the Commission cautioned that "The conclusion that no genocidal policy has been pursued and implemented in Darfur by the Government authorities, directly or through the militias under their control, should not be taken in any way as detracting from the gravity of the crimes perpetrated in that region. International offences such as the crimes against humanity and war crimes that have been committed in Darfur may be no less serious and heinous than genocide."

In March 2005, the Security Council formally referred the situation in Darfur to the Prosecutor of the International Criminal Court, taking into account the Commission report but without mentioning any specific crimes. Two permanent members of the Security Council, the United States and China, abstained from the vote on the referral resolution. As of his fourth report to the Security Council, the Prosecutor has found "reasonable grounds to believe that the individuals identified [in the UN Security Council Resolution 1593] have committed crimes against humanity and war crimes," but did not find sufficient evidence to prosecute for genocide.

In April 2007, the Judges of the ICC issued arrest warrants against the former Minister of State for the Interior, Ahmad Harun, and a Militia Janjaweed leader, Ali Kushayb, for crimes against humanity and war crimes.

On 14 July 2008, prosecutors at the International Criminal Court (ICC), filed ten charges of war crimes against Sudan's President Omar al-Bashir: three counts of genocide, five of crimes against humanity and two of murder. The ICC's prosecutors claimed that al-Bashir "masterminded and implemented a plan to destroy in substantial part" three tribal groups in Darfur because of their ethnicity.

On 4 March 2009, the ICC issued a warrant of arrest for Omar Al Bashir, President of Sudan as the ICC Pre-Trial Chamber I concluded that his position as head of state does not grant him immunity against prosecution before the ICC. The warrant was for war crimes and crimes against humanity. It did not include the crime of genocide because the majority of the Chamber did not find that the prosecutors had provided enough evidence to include such a charge. Later the decision was changed by the Appeals Panel and after issuing the second decision, charges against Omar al-Bashir include three counts of genocide.

Examples

Main article: Genocides in history

For a more comprehensive list, see List of genocides.

 

Naked Soviet POWs held by the Nazis in Mauthausen concentration camp. Political scientist Adam Jones wrote: "[T]he murder of at least 3.3 million Soviet POWs is one of the least-known of modern genocides; there is still no full-length book on the subject in English."

The concept of genocide can be applied to historical events. The preamble of the CPPCG states that "at all periods of history genocide has inflicted great losses on humanity." Revisionist attempts to challenge or affirm claims of genocide are illegal in some countries. Several European countries ban the denial of the Holocaust and the denial of the Armenian genocide, while in Turkey referring to the Armenian genocide, Greek genocide, and Sayfo, and to the period of mass starvation during the Great Famine of Mount Lebanon affecting Maronites, as genocides may be prosecuted under Article 301.

Historian William Rubinstein argues that the origin of 20th-century genocides can be traced back to the collapse of the elite structure and normal modes of government in parts of Europe following World War I, commenting:

The 'Age of Totalitarianism' included nearly all of the infamous examples of genocide in modern history, headed by the Jewish Holocaust, but also comprising the mass murders and purges of the Communist world, other mass killings carried out by Nazi Germany and its allies, and also the Armenian genocide of 1915. All these slaughters, it is argued here, had a common origin, the collapse of the elite structure and normal modes of government of much of central, eastern and southern Europe as a result of the First World War, without which surely neither Communism nor Fascism would have existed except in the minds of unknown agitators and crackpots.

According to Esther Brito, the way in which states commit genocide has evolved in the 21st century and genocidal campaigns have attempted to circumvent international systems designed to prevent, mitigate, and prosecute genocide by adjusting the duration, intensity, and methodology of the genocide. Brito states that modern genocides often happen on a much longer time scale than traditional ones - taking years or decades - and that instead of traditional methods of beatings and executions less directly fatal tactics are used but with the same effect. Brito described the contemporary plights of the Rohingya and Uyghurs as examples of this newer form of genocide. The abuses against West Papuans in Indonesia have also been described as a slow-motion genocide.

Stages, risk factors, and prevention

Main articles: Ten stages of genocide, Risk factors for genocide, and Genocide prevention

Study of the risk factors and prevention of genocide was underway before the 1982 International Conference on the Holocaust and Genocide during which multiple papers on the subject were presented. In 1996 Gregory Stanton, the president of Genocide Watch, presented a briefing paper called "The 8 Stages of Genocide" at the United States Department of State. In it he suggested that genocide develops in eight stages that are "predictable but not inexorable".

The Stanton paper was presented to the State Department, shortly after the Rwandan Genocide and much of its analysis are based on why that genocide occurred. The preventative measures suggested, given the briefing paper's original target audience, were those that the United States could implement directly or indirectly by using its influence on other governments.^{[citation needed]} In 2012, he added two additional stages, discrimination and persecution.

Stage	Characteristics	Preventive measures
1. Classification	People are divided into "us and them".	"The main preventive measure at this early stage is to develop universalistic institutions that transcend... divisions."
2. Symbolization	"When combined with hatred, symbols may be forced upon unwilling members of pariah groups..."	"To combat symbolization, hate symbols can be legally forbidden as can hate speech".
3. Discrimination	"Law or cultural power excludes groups from full civil rights: segregation or apartheid laws, denial of voting rights".	"Pass and enforce laws prohibiting discrimination. Full citizenship and voting rights for all groups."
4. Dehumanization	"One group denies the humanity of the other group. Members of it are equated with animals, vermin, insects, or diseases."	"Local and international leaders should condemn the use of hate speech and make it culturally unacceptable. Leaders who incite genocide should be banned from international travel and have their foreign finances frozen."
5. Organization	"Genocide is always organized... Special army units or militias are often trained and armed..."	"The U.N. should impose arms embargoes on governments and citizens of countries involved in genocidal massacres, and create commissions to investigate violations"
6. Polarization	"Hate groups broadcast polarizing propaganda..."	"Prevention may mean security protection for moderate leaders or assistance to human rights groups...Coups d'état by extremists should be opposed by international sanctions."
7. Preparation	"Victims are identified and separated out because of their ethnic or religious identity..."	"At this stage, a Genocide Emergency must be declared. ..."
8. Persecution	"Expropriation, forced displacement, ghettos, concentration camps".	"Direct assistance to victim groups, targeted sanctions against persecutors, mobilization of humanitarian assistance or intervention, protection of refugees."
9. Extermination	"It is 'extermination' to the killers because they do not believe their victims to be fully human".	"At this stage, only rapid and overwhelming armed intervention can stop genocide. Real safe areas or refugee escape corridors should be established with heavily armed international protection."
10. Denial	"The perpetrators... deny that they committed any crimes..."	"The response to denial is punishment by an international tribunal or national courts"

Other authors have focused on the structural conditions leading up to genocide and the psychological and social processes that create an evolution toward genocide. Ervin Staub showed that economic deterioration and political confusion and disorganization were starting points of increasing discrimination and violence in many instances of genocides and mass killing. They lead to scapegoating a group and ideologies that identified that group as an enemy. A history of devaluation of the group that becomes the victim, past violence against the group that becomes the perpetrator leading to psychological wounds, authoritarian cultures and political systems, and the passivity of internal and external witnesses (bystanders) all contribute to the probability that the violence develops into genocide. Intense conflict between groups that is unresolved, becomes intractable and violent can also lead to genocide. In 2006, Dirk Moses criticised genocide studies due to its "rather poor record of ending genocide".