To date, CKDu (MeN) causes remain undetermined and debatable; nevertheless the number of cases could lead to the application of a precautionary principles from a humanitarian perspective. Due to the fact that the Mesoamerican nephropathy is regarded as a multifactorial disease the experimental design of comparative study should take following logical setting into account.

Multifactorial problem. Assume that a disease is definitely caused by A,B,C. The disease will develop if at least 2 risk factors are present in a certain region.

- formula_1 no prevalence of disease in region 1

- A no prevalence of disease in region 2

- B no prevalence of disease in region 3

- C no prevalence of disease in region 4

- A,B prevalence of disease in region 5

- B,C prevalence of disease in region 6

- C,A prevalence of disease in region 7

- A,B,C prevalence of disease in region 8

Removing the risk factor A in the experimental group in comparison to control group will lead to changes in the outbreak of the disease in only 2 of 8 combinatorically possible regions, even if we define A as a relevant risk factor in this theoretical setting. The same is true if the experimental design adds in a comparative study the risk factor A to the regions in the experimental group in comparison to the control group.

If the difference in experimental and control are 2 risk factors (adding or removing two risk factor e.g. A,B in the control group), then 4 regions will show a differences in prevalence of the disease, with the disadvantage that the experimental design cannot clarify if one or both risk factors A and B are contributing to the progression and prevalence of the disease.

Beside this logical analysis of a multifactorial setting there is space for further investigation, e.g.: Leptospirosis has been suggested as a possible contributing factor and oceanic nephrotoxic algae or agents have also been brought to the chart of possibilities as a culprit for this unusual form of kidney damage..

Assessment of the mentioned risk factors and their possible synergism will depend on more and better research.

The disease can remit spontaneously or become chronic, with exacerbations and remissions. In some persons, it can progress to pulmonary fibrosis and death. About half of cases resolve without treatment or can be cured within 12–36 months, and most within five years. Some cases, however, may persist several decades. Two-thirds of people with the condition achieve a remission within 10 years of the diagnosis. When the heart is involved, the prognosis is generally less favourable, though corticosteroids appear effective in improving AV conduction. The prognosis tends to be less favourable in African Americans than in white Americans.

Some 1990s studies indicated that persons with sarcoidosis appear to be at significantly increased risk for cancer, in particular lung cancer, lymphomas, and cancer in other organs known to be affected in sarcoidosis. In sarcoidosis-lymphoma syndrome, sarcoidosis is followed by the development of a lymphoproliferative disorder such as non-Hodgkin lymphoma. This may be attributed to the underlying immunological abnormalities that occur during the sarcoidosis disease process. Sarcoidosis can also follow cancer or occur concurrently with cancer. There have been reports of hairy cell leukemia, acute myeloid leukemia, and acute myeloblastic leukemia associated with sarcoidosis.

Sometimes, sarcoidosis, even untreated, can be complicated by opportunistic infections.

Experimental infection in immunocompetent and immunocompromised mice has produced intestinal inflammation, altered bowel habits, lethargy and death. Chronic diarrhea has been reported in non-human higher primates.

The exact cause of sarcoidosis is not known. The current working hypothesis is, in genetically susceptible individuals, sarcoidosis is caused through alteration to the immune response after exposure to an environmental, occupational, or infectious agent. Some cases may be caused by treatment with TNF inhibitors like etanercept.

Adding elements to the debate, another recent study from Sri Lanka, where a similar and apparently new form of CKDu has become a serious public health concern too, suggests chronic synergestic exposure to multiple pesticide residues and heavy metal could be the main causal factor. The authors hypothesize that “Agrochemicals are the essential factor for the disease“. Dr. Channa Jayasumana, a Sri Lankan researcher, member of the medical faculty of Rajarata University, has been a leading supporter of the pesticide hypothesis, always in connection to hard water consumption. He has said that research conducted by his university found that “pesticides and chemical fertilizers were responsible for the spike in kidney diseases”, Further he points out heat stress and dehydration is an important aggravating factor of the disease.

Infection is through contaminated material such as earth, water, uncooked or cross-contaminated food that has been in contact with the feces of an infected individual or animal. Contact must then be transferred to the mouth and swallowed. It is especially prevalent amongst those in regular contact with bodies of fresh water including recreational water such as swimming pools. Other potential sources include insufficiently treated water supplies, contaminated food, or exposure to feces. The high resistance of "Cryptosporidium" oocysts to disinfectants such as chlorine bleach enables them to survive for long periods and still remain infective. Some outbreaks have happened in day care related to diaper changes.

The following groups have an elevated risk of being exposed to "Cryptosporidium":

- Child care workers

- Parents of infected children

- People who take care of other people with cryptosporidiosis

- International travelers

- Backpackers, hikers, and campers who drink unfiltered, untreated water

- People, including swimmers, who swallow water from contaminated sources

- People who handle infected cattle

- People exposed to human feces through sexual contact

Cases of cryptosporidiosis can occur in a city that does not have a contaminated water supply. In a city with clean water, it may be that cases of cryptosporidiosis have different origins. Testing of water, as well as epidemiological study, are necessary to determine the sources of specific infections. "Cryptosporidium" is causing serious illness more frequently in immunocompromised than in apparently healthy individuals. It may chronically sicken some children, as well as adults who are exposed and immunocompromised. A subset of the immunocompromised population is people with AIDS. Some sexual behaviors can transmit the parasite directly.

Blastocystis colonisation is positively associated with irritable bowel syndrome (IBS) and is a possible risk factor for developing IBS. A study of IBS patients in the Middle East showed a "significantly increased" immune reaction in IBS patients to "Blastocystis", even when the organism could not be identified in stool samples.

The following reports have linked "Blastocystis" infection to inflammatory bowel disease:

- A study using riboprinting identified specific types of "Blastocystis" as associated with inflammation.

- A case report described inflammatory bowel disease in conjunction with "Blastocystis" infection.

- Three research groups have reported experimental infection of mice with "Blastocystis" produces intestinal inflammation.

- An article in a non-peer reviewed medical journal noted that the increase in "Blastocystis" case reports coincided with reported increases in the prevalence of inflammatory bowel disease from several European countries.

Cryptosporidiosis is found worldwide. It causes 50.8% of water-borne diseases that are attributed to parasites. In developing countries, 8–19% of diarrheal diseases can be attributed to "Cryptosporidium". Ten percent of the population in developing countries excretes oocysts. In developed countries, the number is lower at 1–3%. The age group most affected are children from 1 to 9 years old.

Roughly 30% of adults in the United States are seropositive for cryptosporidiosis, meaning that they contracted the infection at some point in their lives.

A wide variety of clinical signs have been described for HS in cattle and buffaloes. The incubation periods (the time between exposure and observable disease) for buffalo calves 4–10 months of age varies according to the route of infection. The incubation period is 12–14 hours, approximately 30 hours and 46–80 hours for subcutaneous infection, oral infection and natural exposure, respectively.

There is variability in the duration of the clinical course of the disease. In the case of experimental subcutaneous infection, the clinical course lasted only a few hours, while it persisted for 2–5 days following oral infection and in buffaloes and cattle that had been exposed to naturally-infected animals. It has also been recorded from field observations that the clinical courses of per-acute and acute cases were 4–12 hours and 2–3 days, respectively.

Generally, progression of the disease in buffaloes and cattle is divided into three phases. Phase one is characterised by fever, with a rectal temperature of , loss of appetite and depression. Phase two is typified by increased respiration rate (40–50/minute), laboured breathing, clear nasal discharge (turns opaque and mucopurulent as the disease progresses), salivation and submandibular oedema spreading to the pectoral (brisket) region and even to the forelegs. Finally, in phase three, there is typically recumbency, continued acute respiratory distress and terminal septicaemia. The three phases overlap when the disease course is short. In general, buffaloes have a more acute onset of disease than cattle, with a shorter duration.

Mortality rate in treated cases

- 0-2% in treated cases among immunocompetent patients

- 29% in immunocompromised patients

- 40% in the subgroup of patients with AIDS

- 68% in patients presenting as acute respiratory distress syndrome (ARDS)

Haemorrhagic septicaemia is one of the most economically important pasteurelloses. Haemorrhagic septicaemia in cattle and buffaloes was previously known to be associated with one of two serotypes of "P. multocida": Asian B:2 and African E:2 according to the Carter-Heddleston system, or 6:B and 6:E using the Namioka-Carter system.

The disease occurs mainly in cattle and buffaloes, but has also been reported in goats ("Capra aegagrus hircus"), African buffalo ("Syncerus nanus"), camels, horses and donkeys ("Equus africanus asinus"), in pigs infected by serogroup B, and in wild elephants ("Elephas maximus"). Serotypes B:1 and B:3,4 have caused a septicaemic disease in antelope ("Antilocapra americana") and elk ("Cervus canadensis"), respectively. Serotype B:4 was associated with the disease in bison ("Bison bison").

Serotypes E:2 and B:2 were associated with HS outbreaks in Africa and Asia respectively. Serotype E:2 was reported in Senegal, Mali, Guinea, Ivory Coast, Nigeria, Cameroon, the Central African Republic and Zambia. However, it is now inaccurate to associate outbreaks in Africa with serotype E:2 as many outbreaks of HS in Africa have now been associated with serogroup B. In the same manner, serogroup E has been associated with outbreaks in Asia. For instance, one record of "Asian serotype" (B:2) was reported in Cameroon. Some reports showed that serotype B:2 may be present in some East African countries. Both serogroups B and E have been reported in Egypt and Sudan.

Natural routes of infection are inhalation and/or ingestion. Experimental transmission has succeeded using intranasal aerosol spray or oral drenching. When subcutaneous inoculation is used experimentally, it results in rapid onset of the disease, a shorter clinical course and less marked pathological lesions compared to the longer course of disease and more profound lesions of oral drenching and the intranasal infection by aerosols.

When HS was introduced for the first time into a geographic area, morbidity and mortality rates were high, approaching 100% unless animals were treated in the very early stages of disease.

Sex is another factor inconstantly linked to contraction of blastomycosis: though many studies show more men than women affected, some show no sex-related bias. As mentioned above, most cases are in middle aged adults, but all age groups are affected, and cases in children are not uncommon.

Kashin–Beck disease occurrence is limited to 13 provinces and two autonomous regions of China. It has also been reported in Siberia and North Korea, but incidence in these regions is reported to have decreased with socio-economic development. In China, KBD is estimated to affect some 2 million to 3 million people across China, and 30 million are living in endemic areas. Life expectancy in KBD regions has been reported to be significantly decreased in relation to selenium deficiency and Keshan disease (endemic juvenile dilative cardiomyopathia).

The prevalence of KBD in Tibet varies strongly according to valleys and villages.

Prevalence of clinical symptoms suggestive of KBD reaches 100% in 5- to 15-year-old children in at least one village. Prevalence rates of over 50% are not uncommon. A clinical prevalence survey carried out in Lhasa prefecture yielded a figure of 11.4% for a study population of approximately 50,000 inhabitants. As in other regions of China, farmers are by far the most affected population group.

Chagas disease affects 8 to 10 million people living in endemic Latin American countries, with an additional 300,000–400,000 living in nonendemic countries, including Spain and the United States. An estimated 41,200 new cases occur annually in endemic countries, and 14,400 infants are born with congenital Chagas disease annually. in 2010 it resulted in approximately 10,300 deaths up from 9,300 in 1990.

The disease is present in 18 countries on the American continents, ranging from the southern United States to northern Argentina. Chagas exists in two different ecological zones. In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where triatomines breed and feed on the more than 150 species from 24 families of domestic and wild mammals, as well as humans, that are the natural reservoirs of "T. cruzi".

Although Triatominae bugs feed on them, birds appear to be immune to infection and therefore are not considered to be a "T. cruzi" reservoir. Even when colonies of insects are eradicated from a house and surrounding domestic animal shelters, they can re-emerge from plants or animals that are part of the ancient, sylvatic (referring to wild animals) infection cycle. This is especially likely in zones with mixed open savannah, with clumps of trees interspersed by human habitation.

The primary wildlife reservoirs for "Trypanosoma cruzi" in the United States include opossums, raccoons, armadillos, squirrels, woodrats, and mice. Opossums are particularly important as reservoirs, because the parasite can complete its life cycle in the anal glands of this animal without having to re-enter the insect vector. Recorded prevalence of the disease in opossums in the U.S. ranges from 8.3% to 37.5%.

Studies on raccoons in the Southeast have yielded infection rates ranging from 47% to as low as 15.5%. Armadillo prevalence studies have been described in Louisiana, and range from a low of 1.1% to 28.8%. Additionally, small rodents, including squirrels, mice, and rats, are important in the sylvatic transmission cycle because of their importance as bloodmeal sources for the insect vectors. A Texas study revealed 17.3% percent "T. cruzi" prevalence in 75 specimens representing four separate small rodent species.

Chronic Chagas disease remains a major health problem in many Latin American countries, despite the effectiveness of hygienic and preventive measures, such as eliminating the transmitting insects. However, several landmarks have been achieved in the fight against it in Latin America, including a reduction by 72% of the incidence of human infection in children and young adults in the countries of the Southern Cone Initiative, and at least three countries (Uruguay, in 1997, and Chile, in 1999, and Brazil in 2006) have been certified free of vectorial and transfusional transmission. In Argentina, vectorial transmission has been interrupted in 13 of the 19 endemic provinces, and major progress toward this goal has also been made in both Paraguay and Bolivia.

Screening of donated blood, blood components, and solid organ donors, as well as donors of cells, tissues, and cell and tissue products for "T. cruzi" is mandated in all Chagas-endemic countries and has been implemented. Approximately 300,000 infected people live in the United States, which is likely the result of immigration from Latin American countries, and there have been 23 cases acquired from kissing bugs in the United States reported between 1955 and 2014. With increased population movements, the possibility of transmission by blood transfusion became more substantial in the United States. Transfusion blood and tissue products are now actively screened in the U.S., thus addressing and minimizing this risk.

Much of the deadliness of the epidemic in Sub-Saharan Africa is caused by a deadly synergy between HIV and tuberculosis, termed a "co-epidemic". The two diseases have been "inextricably bound together" since the beginning of the HIV epidemic. "Tuberculosis and HIV co-infections are associated with special diagnostic and therapeutic challenges and constitute an immense burden on healthcare systems of heavily infected countries like Ethiopia." In many countries without adequate resources, the tuberculosis case rate has increased five to ten-fold since the identification of HIV. Without proper treatment, an estimated 90 percent of persons living with HIV die within months after contracting tuberculosis. The initiation of highly active antiretroviral therapy in persons coinfected with tuberculosis can cause an immune reconstitution inflammatory syndrome with a worsening, in some cases severe worsening, of tuberculosis infection and symptoms.

An estimated 874,000 people in Sub-Saharan Africa were living with both HIV and tuberculosis in 2011, with 330,000 in South Africa, 83,000 in Mozambique, 50,000 in Nigeria, 47,000 in Kenya, and 46,000 in Zimbabwe. In terms of cases per 100,000 population, Swaziland's rate of 1,010 was by far the highest in 2011. In the following 20 African countries, the cases-per-100,000 coinfection rate has increased at least 20 percent between 2000 and 2011: Algeria, Angola, Chad, Comoros, Republic of the Congo, Democratic Republic of the Congo, Equatorial Guinea, The Gambia, Lesotho, Liberia, Mauritania, Mauritius, Morocco, Mozambique, Senegal, Sierra Leone, South Africa, Swaziland, Togo, and Tunisia.

Since 2004, however, tuberculosis-related deaths among people living with HIV have fallen by 28 percent in Sub-Saharan Africa, which is home to nearly 80 percent of the people worldwide who are living with both diseases.

Although no treatment has been found it has been shown that affected individuals benefit considerably from rehabilitation and use of adequate walking aids. In the Central African Republic some children have been operated with an elongation of the Achilles tendon which improved the position of the foot but the long term consequence remains uncertain.

There is currently no vaccine against Chagas disease. Prevention is generally focused on decreasing the numbers of the insect that spreads it ("Triatoma") and decreasing their contact with humans. This is done by using sprays and paints containing insecticides (synthetic pyrethroids), and improving housing and sanitary conditions in rural areas. For urban dwellers, spending vacations and camping out in the wilderness or sleeping at hostels or mud houses in endemic areas can be dangerous; a mosquito net is recommended. Some measures of vector control include:

- A yeast trap can be used for monitoring infestations of certain species of triatomine bugs ("Triatoma sordida", "Triatoma brasiliensis", "Triatoma pseudomaculata", and "Panstrongylus megistus").

- Promising results were gained with the treatment of vector habitats with the fungus "Beauveria bassiana".

- Targeting the symbionts of Triatominae through paratransgenesis can be done.

A number of potential vaccines are currently being tested. Vaccination with "Trypanosoma rangeli" has produced positive results in animal models. More recently, the potential of DNA vaccines for immunotherapy of acute and chronic Chagas disease is being tested by several research groups.

Blood transfusion was formerly the second-most common mode of transmission for Chagas disease, but the development and implementation of blood bank screening tests has dramatically reduced this risk in the 21st century. Blood donations in all endemic Latin American countries undergo Chagas screening, and testing is expanding in countries, such as France, Spain and the United States, that have significant or growing populations of immigrants from endemic areas. In Spain, donors are evaluated with a questionnaire to identify individuals at risk of Chagas exposure for screening tests.

The US FDA has approved two Chagas tests, including one approved in April 2010, and has published guidelines that recommend testing of all donated blood and tissue products. While these tests are not required in US, an estimated 75–90% of the blood supply is currently tested for Chagas, including all units collected by the American Red Cross, which accounts for 40% of the U.S. blood supply. The Chagas Biovigilance Network reports current incidents of Chagas-positive blood products in the United States, as reported by labs using the screening test approved by the FDA in 2007.

The character of the neurological injury is not clear. The disease onset is associated with high intake of cyanide from a monotonous diet of bitter cassava, which is low in protein, particularly sulfur amino acids. These are essential for the detoxification in the body of cyanide to thiocyanate, which is removed in the urine. A number of studies implicate the combination of high cyanide intake from bitter cassava and low intake of sulfur amino acids as the cause. It has now been shown that the month by month incidence of konzo is significantly correlated with the percentage of children with high urinary thiocyanate content, which is a measure of their cyanide intake. The importance of an adequate supply of protein sulfur amino acids is shown from three unrelated konzo epidemics in Mozambique, Tanzania and DRC. People of the same ethnic group living only 5 km away from those with konzo had near zero konzo prevalence, because in Mozambique they lived near the sea, in Tanzania they lived near Lake Victoria and had access to fish and in DRC they lived near the forest and had access to animal protein.

The dose-response relationship between konzo incidence and cyanide intake, together with the prevention of konzo in many villages by reducing cyanide intake from cassava (see below) and the importance of sulfur amino acids in prevention of konzo, shows that konzo is very likely due to high cyanide/low sulfur amino acid intake in a diet of bitter cassava. Konzo does not occur unless these conditions are met, which occurs only in remote villages in six tropical African countries. The total number of reported cases up to 2009 was 6788, but most cases are never reported and there was an estimate of 100,000 cases in DRC alone in 2002. Konzo is spreading geographically as cassava is being grown in new areas where there is little knowledge of processing methods to remove cyanogens. Konzo epidemics occur due to war which causes disruption of life in poor villages and drought, when the plant increases the cyanogen content of roots 2-4 times and the cyanide content of cassava flour also increases greatly. Konzo is also endemic in certain areas.

Traditional methods of processing cassava to remove cyanogens consist of sun drying and heap fermentation in East Africa, which are inadequate in removal of cyanogens even in a year of normal rainfall. In Central Africa soaking (retting) of cassava roots in water for 4–5 days is adequate, but short soaking for 1–2 days leaves large amounts of cyanogens in flour and leads to konzo. In West Africa a roasted product called gari is produced by a different method than that used to produce flour, which reduces the total cyanide content to 10-20 ppm. There are no reported cases of konzo west of Cameroon. However another neurological disease called tropical ataxic neuropathy (TAN), occurs amongst older people in south-west Nigeria, Tanzania, Uganda, Kenya, West Indies and South India, and is probably due to long term intake of cyanogens from cassava at a lower level than that needed to cause konzo.

Although it is not clear what causes LS, several theories have been postulated. Lichen Sclerosus is not contagious; it cannot be caught from another person.

Several risk factors have been proposed, including autoimmune diseases, infections and genetic predisposition. There is evidence that LS can be associated with thyroid disease.

Lichen sclerosus may have a genetic component. Higher rates of lichen sclerosus have been reported among twins and among family members.

Until recently humans and water fleas ("Cyclops") were regarded as the only animals this parasite infects. It has been shown that baboons, cats, dogs, frogs and catfish ("Synodontis") can also be infected naturally. Ferrets have been infected experimentally.

HIV infection rates in central Africa are generally moderate to high.

Dracunculiasis is caused by drinking water contaminated by water fleas that host the "D. medinensis" larvae. Dracunculiasis has a history of being very common in some of the world's poorest areas, particularly those with limited or no access to clean water. In these areas, stagnant water sources may still host copepods, which can carry the larvae of the guinea worm.

After ingestion, the copepods die and are digested, thus releasing the stage 3 larvae, which then penetrate the host's stomach or intestinal wall, and then enter into the abdominal cavity and retroperitoneal space. After maturation, which takes approximately three months, mating takes place; the male worm dies after mating and is absorbed by the host's body.

Approximately one year after mating, the fertilized females migrate in the subcutaneous tissues adjacent to long bones or joints of the extremities. They then move towards the surface, resulting in blisters on the skin, generally on the distal lower extremity (foot). Within 72 hours, the blister ruptures, exposing one end of the emergent worm. The blister causes a very painful burning sensation as the worm emerges, and the sufferer will often immerse the affected limb in water to relieve the burning sensation. When a blister or open sore is submerged in water, the adult female releases hundreds of thousands of stage 1 guinea worm larvae, thereby contaminating the water.

During the next few days, the female worm can release more larvae whenever it comes in contact with water, as it extends its posterior end through the hole in the host's skin. These larvae are eaten by copepods, and after two weeks (and two molts), the stage 3 larvae become infectious and, if not filtered from drinking water, will cause the cycle to repeat. Infected copepods can live in the water for up to four months.

The male guinea worm is typically much smaller () than the female, which, as an adult, can grow to long and be as thick as a spaghetti noodle.

Infection does not create immunity, so people can repeatedly experience Dracunculiasis throughout their lives. Several worms may emerge simultaneously; the average is 1.8. Up to 14 worms have been reported in one individual.

In drier areas just south of the Sahara desert, cases of the disease often emerge during the rainy season, which for many agricultural communities is also the planting or harvesting season. Elsewhere, the emerging worms are more prevalent during the dry season, when ponds and lakes are smaller and copepods are thus more concentrated in them. Guinea worm disease outbreaks can cause serious disruption to local food supplies and school attendance.

The infection can be acquired by eating a fish paratenic host, but this is rare. No reservoir hosts are known; that is, each generation of worms must pass through a human – or possibly a dog.

Rabbits helped keep vegetation in their environments short through grazing and short grasses are conducive to habitation by the butterfly, "Plebejus argus""." When the population of rabbits experienced a decline due to Myxomatosis, grass lengths increased, limiting the environments in which "P. argus" could live, thereby contributing to the decline of the butterfly population.

Pregnancy has been reported to exacerbate LAM in some cases. However, the risk has not been rigorously studied. In a survey of 318 patients who indicated that they had had at least one pregnancy, 163 responded to a second survey focusing on lung collapse. A total of 38 patients reported a pneumothorax with pregnancy, consistent with an incidence of pneumothorax in pregnancy of at least 10% (38 of 318). In one third of patients, the pneumothorax during pregnancy led to the LAM diagnosis. Pneumothoraces were almost twice as frequent on the right as on the left, and four women presented with bilateral spontaneous pneumothorax. Most pneumothoraces took place during the second and third trimesters. This study and others suggest that pregnancy is associated with pleural complications in LAM patients. Few women with a known LAM diagnosis choose to become pregnant and patients in whom LAM is diagnosed during pregnancy rarely have baseline pulmonary function tests available, complicating resolution of this question.