Mystery Kidney Disease in Nicaragua

Kidney failure in men is a lot more common in Nicaragua than in North America. The usual causes in Canada and the US are high blood pressure and diabetes, but these are not the explanation in Nicaragua.

Dialysis and transplantation are not practical options in Nicaragua, so when a young man develops end stage kidney failure, this means the individual will die.

Nicaragua is struggling to offer basic primary care and does not have the resources to investigate this serious health problem. International interest has resulted in some research and a variety of risk factors have been identified. I did a Google Scholar literature search with the words kidney and Nicaragua, and 15 articles were identified in the world medical literature.

A 2010 article reported on a community based survey of individuals in five villages in Northwest Nicaragua. Eighteen (18) percent of the men in the community had an abnormal serum creatinine, which is the main laboratory marker of kidney failure. This is six times higher than the prevalence in Canada!

Occupation appears to have a major influence on the prevalence. The table below shows the differences in prevalence of an abnormal serum creatinine by occupation.

Occupation	Percent
all men	18
subsistence farmer	26
banana/sugarcane worker	22
construction worker	15
fisherman	13
coffee worker	7
service industry worker	0

Other reports have also noted the higher prevalence in the farming and sugarcane sectors.

Age is clearly a factor. The prevalence increases with age.

Dehydration is a commonly reported consideration, which makes perfect sense, because as dehydration worsens, blood flow to the kidney decreases, and the risk of kidney damage increases. One article reported that sugarcane workers are paid based on how many tons of sugarcane they harvest. The incentive is therefore to work longer hours and to take fewer breaks, which results in more severe dehydration. The same report noted that some men lose up to 5 pounds over a work day! Fear of contaminated water might be another reason why the workers drink so little. Makes no sense, since better hydration would improve their mental alertness and physical energy. Sounds crazy that men would continue to work while so thirsty, but I can imagine that this does happen. History is replete with workers suffering under terrible conditions to earn a living for their family.

Likely there are additional factors. Pesticides are mentioned as a possible kidney toxin. The plantations in Nicaragua use chemicals that are banned in Canada. Modern safety precautions to protect workers are not usually practiced.

Treatment with diuretic, non-steroidal anti-inflammatory, and antibiotic medications might play a role. These are common treatments for "urine infection" in Nicaragua.

The general population knows about the Mystery Kidney Disease, and the populace is worried. I experienced this concern in my previous visits. Many mothers wanted me to check their child for urine infection. This heightened concern for urine problems perplexed me at first, but once I learned about the Mystery Kidney Disease problem, I understood.

The at-risk men who work as sugarcane workers often complain of chistata. A common symptom of chistata is discomfort with voiding. Discomfort with voiding is a typical symptom of infection in the bladder or urethra, but this is also a symptom associated with severe dehydration because the urine is very concentrated (dark) and in this situation, tiny crystals of calcium, phosphate, oxalate, or uric acid can precipitate out in the urine, and these crystals can be painful to pass. However, the discomfort with voiding in men with chistata is mostly presumed to be due to urine infection and since some of these men develop kidney failure, there is a common perception that the kidney failure is due to urine infection. The general population believe this and so do the many of the physicians.

The physicians I met on prior visits commonly over treat children and adults for possible urinary tract infection. Any urine symptom at all, or any positive urine dipstick test is usually treated with an antibiotic. This didn't make any sense to me and my first thought was that the medical education system in Nicaragua was to blame for the over-diagnosis and over-treatment. Now, I realize that the physicians might not be any more objective than the mothers! A recent article confirms my observations. Based on interviews, the study reported that pharmacists and physicians commonly prescribed antibiotics for individuals with "chistata." Other commonly prescribed medications included diuretics and non-steroidal anti-inflammatory agents. All of these medications are potentially toxic to the kidneys, especially in a dehydrated individual. It is possible, therefore, that local treatment practices are a factor! A very plausible scenario for the Mystery Kidney Disease might be repeated episodes of dehydration, treatment with medications toxic to the kidney while dehydrated, and time. 

Since Gigante, the community where I will help out as a paediatrician, is a fishing village, and since fishermen are at risk, during a visit I will talk to the mothers about the vital importance of hydration. As with families everywhere, if the mother understands, there is a good chance that all the family members will benefit.

References

Torres C et al. Decreased Kidney Function of Unknown Cause in Nicaragua: A Community-Based Survey. AJKD 2010;55:485-96.

Ramirez-Rubio O et al. Chronic Kidney Disease in Nicaragua: a Qualitative Analysis of Semi-structured Interviews with Physicians and Pharmacists. BMC Public Health 2013;13:350

Preventing Dental Disease in Nicaragua

Tooth decay is a worldwide problem, and dental hygiene is an important part of preventative care for every child.

With our trips this winter, courtesy of a generous donation from Sierra Dental, we will help provide preventative dental care for every child we see in the new clinic in Gigante, Nicaragua.

Anneline Webb is the Director of the Before and After School Care Program at Alexander Ferguson Elementary School in Calgary. Prior to this position, Anneline served with distinction as my assistant in The Childrens' Clinic. Denae Webb, Anneline's beautiful daughter, attends Alexander Ferguson. Her friend, Zoe Waxmann, also attends the school. Zoe's Mom, Clarissa Waxmann, heard about the planning for our trips to Nicaragua this winter, and she decided she wanted to help. Clarissa Waxmann works at Sierra Dental, a popular full service dental clinic in SW Calgary, and she arranged a donation of toothbrushes and dental floss. Thank you Anneline and Denae, Clarissa and Zoe, and Sierra Dental for arranging this thoughtful donation.

Thank you Clarissa Waxmann and Sierra Dental!

Breakbone Fever

AKA Dengue Fever. The name fits, because the bone pain suffered by some individuals is severe.

Nicaragua Dispatch, an online English-language newspaper, ran this headline October 30, 2013 
- Dengue Claims 14th Victim in Nicaragua. 
The headline a week earlier on October 24, 2013 - Nicaragua on Red Alert for Dengue.
After reading these articles, a review of Dengue seemed prudent. 

Dengue is caused by a virus and there are four different serotypes. Individuals who live in an endemic region such as Nicaragua are usually infected by several or all of the strains over their lifetime.

In 2004 a prospective study of about 3800 children, 2 to 9 years of age, was started in Managua, the capital of Nicaragua. The children had annual blood tests to identify infection with dengue virus. Over the first four years of the study, 22 to 40% of the two year-olds and 90 to 95% of the nine year-olds showed evidence of Dengue. So, every child is eventually infected.

Infection with one dengue serotype confers lifelong immunity, but only to that serotype. Most adults are immune.

The virus is transmitted by a female Aedes mosquito. These mosquitoes thrive in stagnant water such as might be found in old tires or other small containers around a home.

The mosquitoes acquire the virus when they feed (bite) an individual already infected with the virus. The mosquito can immediately transmit the virus if the insect bites another individual, which is common, and which accounts for epidemics. Entire families often develop infection within a 24 to 36 hour period, presumably from the bites of a single infected female mosquito.

Once inoculated into a human, dengue has an incubation period of 3 to 14 days (average 4 to 7 days).

The majority (50 to 90%) of infected individuals have no symptoms and do not realize they are infected. Data from a 1997 Cuban epidemic suggest that for every symptomatic case of dengue fever, there are 14 unrecognized cases.

Classic dengue fever is defined by the Pan American Health Organization (PAHO) as an acute febrile illness of 2 to 7 days duration associated with two or more of the following - severe headache, pain behind the eyes, severe muscle pain, joint pain, characteristic rash, hemorrhagic manifestations, low white blood cell count.

Many patients experience a prodrome of chills, red mottling of the skin, and facial flushing, which is considered a sensitive and specific indicator of dengue fever. The prodrome might last for 2 to 3 days. The illness presents with the rapid onset of high fever. The fever might reach 41°C. In addition to the symptoms and signs above, the patient might also have weakness, vomiting, sore throat, or altered taste sensation. The rash is a centrifugal, maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin sparing. The rash typically begins on day 3 and persists 2-3 days. Fever typically resolves with the cessation of viremia.

Leukopenia and thrombocytopenia are common findings in dengue fever and might be caused by direct destructive actions of the virus on bone marrow precursor cells. Approximately one third of patients with dengue fever have mild hemorrhagic symptoms, including petechiae, gingival bleeding, and a positive tourniquet test.

Dengue fever is typically a self-limiting disease with a mortality rate of less than 1%. Supportive care with analgesics, fluid replacement, and bed rest is usually sufficient. Acetaminophen can be used to treat fever and relieve other symptoms. Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids should not be used.

A small percentage of persons who were previously infected by one dengue serotype and who are later infected with a second serotype, develop the potentially fatal complications
Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). The severity of the secondary dengue infection appears to intensify as the interval increases between the infections.

When a previously infected individual is later infected with a different serotype, non-neutralizing antibodies recognize the dengue virus but do not neutralize or inhibit virus replication. Instead, the virus and antibody form an antigen-antibody complex. This complex is recognized by receptors on macrophages, which then internalize the immune complex and allow the virus to replicate unchecked. This phenomenon is called antibody-dependent enhancement. The affected macrophages release vasoactive mediators that increase vascular permeability. This serious complication usually develops just as the dengue fever episode is resolving.

Abdominal pain in conjunction with restlessness, change in mental status, hypothermia, and a drop in the platelet count presages the development of DHF.

Ninety percent of patients with DHF are younger than 15 years of age.

In persons with DHF, the fever reappears, as a biphasic or "saddleback" fever curve. Along with this biphasic fever, patients with DHF have more obvious hemorrhagic manifestations and plasma leakage. The critical feature of DHF is plasma leakage. Plasma leakage is caused by increased capillary permeability. Bleeding is caused by capillary fragility and thrombocytopenia. DSS is essentially DHF with progression into circulatory failure, with ensuing hypotension, and, ultimately, shock and death. Death can occur within 8-24 hours after onset of signs of circulatory failure. The most common clinical findings with impending shock include hypothermia, abdominal pain, vomiting, and restlessness. DHF has a mortality rate of 2-5% when treated and up to 50% when not treated. In the October 24th Nicaragua Dispatch article, Sonia Castro, the Sandinista Minister of Health, is quoted,

I want the population to know that if they are showing serious signs of dengue, there is a 50% chance they could die even if they are in the health clinic. So we have to destroy the mosquitos' nests for breeding.

This statement is an official acknowledgement that the health care available in Nicaragua is not sufficient to offer the modern intensive medical care necessary. If you live in Canada, the mortality rate is 2 to 5%. If you live in Nicaragua, the mortality rate is 50%. 

The only treatment is supportive care with hydration, blood pressure support with pressors, and platelets and plasma for bleeding. No specific antiviral medication is available.

Prevention is therefore fundamental for control.

Nicaragua insecticide spray program in operation. 

The worker is not wearing a mask. Ouch!!!!! 

Photo courtesy of Nicaragua Dispatch.

The mosquito that transmits the virus bites only by day so mosquito nets are of limited use. Only takes one bite, and the ankles and the back of the neck are the preferred sites.

The only way to prevent dengue virus is to avoid bites. Susceptible individuals should wear N,N-diethyl-3-methylbenzamide (DEET)–containing mosquito repellent and protective clothing, preferably impregnated with permethrin insecticide. They should choose well-screened or air-conditioned places. Larval habitats (stagnant water) should be eliminated or treated with larvacides. Indoor sprays should be considered to eliminate mosquitoes.

References

Trends in Patterns of Dengue Transmission over 4 Years in a Pediatric Cohort Study in Nicaragua. J Infect Dis. 2010;201:5-14.

Nicaragua Dispatch 
http://www.nicaraguadispatch.com/news/2013/10/dengue-claims-14th-victim-in-nicaragua/8301

eMedicine
http://emedicine.medscape.com/article/215840-overview

Worms in Nicaragua

Worms in Nicaragua


Worm disease is common in Nicaragua. One study showed Ascaris infection in 13% of individuals.

Worms are present worldwide in the moist warm soil found in the tropical latitudes. There are three common worms, Ascaris lumbricoides, Trichuris trichiura (whipworm), and Anclostoma duodenale & Necator americanus (hookworm).

 Ascaris eggs on R & L. Adult female in center. Images courtesy CDC.

Ascaris live in the lumen of the small intestine. A female can produce approximately 200,000 eggs per day, which are passed with the feces. Fertile eggs are infective after 18 days to several weeks, depending on the environmental conditions. After infective eggs are swallowed, the larvae hatch, invade the intestinal mucosa, and are carried via the blood to the lungs. The larvae mature further in the lungs (10 to 14 days), penetrate the alveolar walls, ascend the bronchial tree to the throat, and are swallowed. Upon reaching the small intestine, they develop into adult worms. Between 2 and 3 months are required from ingestion of the infective eggs to oviposition by the adult female. Adult worms can live 1 to 2 years.

Hookworm larva. Images courtesy CDC.

Hookworm eggs are passed in the stool, and the larvae hatch in 1 to 2 days. The larvae are infective after 5 to 10 days, and can survive 3 to 4 weeks. On contact with the human host (bare feet), the larvae penetrate the skin and are carried through the blood vessels to the heart and then to the lungs. They penetrate into the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed. The larvae reach the small intestine, where they mature into adults. Adult worms attach to the intestinal wall with resultant blood loss. Most adult worms are eliminated within 1 to 2 years.

Whipworm eggs on R & L. Adult female in center. Images courtesy CDC.

Whipworm eggs are passed in the stool, and the eggs are infective in 15 to 30 days. The eggs hatch in the small intestine and release larvae that mature and migrate to the colon. Female worms in the cecum shed between 3,000 and 20,000 eggs per day. The lifespan of an adult is about 1 year.

Once infected with a worm, a child can develop abdominal pain and distension, intestinal obstruction, iron-deficiency anemia, malnutrition and poor growth, and allergic reactions.

Mebendazole kills the worms. Mebendazole is on the World Health Organization (WHO) List of Essential Medicines for Children, and is intended for the use in children up to 12 years of age. There is limited data on the safety in children under the age of 2 years. In Nicaragua, a government program is in place to administer the medication. Each school-aged child receives a 500 mg dose of mebendazole. Reinfection is common, so the medication needs to be re-administered. 

Prevention is preferable to regular re-administration of the medication. 

The fundamentals of prevention for all worms include access to clean water, modern sanitation to dispose of infected feces, good personal hygiene with regular hand washing, and careful cleansing of soil-grown-vegetables and fruits.

To prevent hookworm infection, individuals should not walk barefoot in the soil and should otherwise avoid skin contact with soil.

Parasites in Nicaragua

Parasites in Nicaragua

Intestinal parasites in Nicaragua are endemic and contaminated water is the most common source. The common parasites include Entamoeba histolytica, Giardia lamblia, and Cryptosporium species. 

In one recent study, 53% of tested wells in Nicaragua contained amoeboflagellates. A study of 480 apparently healthy individuals in Leon, Nicaragua reported that Entamoeba histolytica or Entamoeba dispar was present in 12% of stool specimens. Another study found that Entamoeba histolytica or Entamoeba dispar was present in 19% of individuals and that Giardia lamblia was present in 16%. These percentages are high enough, that all rural children who drink well water should be presumed to have parasites in their intestine.

Infection by Giardia lamblia occurs by ingestion of mature cysts from fecally contaminated food, water, or hands. Swallowing as few as 10 cysts is enough to cause illness. The cysts are hardy and can survive several months in cold water. The symptoms of giardiasis normally begin 1 to 3 weeks after a person has been infected.

Giardia lamblia trophozoites L & R images, cyst in center. Images courtesy of CDC.

Infection by Entamoeba histolytica occurs by ingestion of mature cysts in fecally contaminated food, water, or hands. Although Entamoeba histolytica is commonly found in the stool, the majority of individuals are not symptomatic, but are potential carriers (able to transmit parasite but not symptomatic). About 10% of individuals develop amoebic dysentery. Amoebic dysentery has a gradual onset with watery or bloody diarrhea, crampy abdominal pain, and poor appetite and weight loss. Liver abscess is a possible complication. The infection is more common and more severe in malnourished children. 

Entamoeba histolytica trophozoites with ingested red blood cells. Images courtesy CDC.

Amoebic dysentery and giardiasis are treated with metronidazole. Unless the source of the infection is eliminated, many individuals will be re-infected after treatment. 

Prevention is therefore important. To prevent infection, the contaminated water source needs to be eliminated or the water needs to be treated. Drinking only bottled water is a good idea but might be too expensive for the average Nicaraguan family. Water can treated in a variety of ways shown in the table below. Careful hand washing and cleaning uncooked vegetables and fruits with clean or treated water is important.

	Boiling	Filter 1 micron	Chemical	Solar Irradiation
Entamoeba histolytica	Yes	Yes	Yes	?
Giardia lamblia	Yes	Yes	No	?
Cryptosporidium species	Yes	Yes/No	No	?

For chemical disinfection, two drops of bleach per liter of water is sufficient. Let the treated water stand for at least thirty minutes. Chemical disinfection is not sufficient for Giardia lamblia or Cryptosporidium. 

Not all filtration systems work for Cryptosporidium. A filtration system is adequate for Cryptosporidium only if the description includes one of the following three statements - reverse osmosis, absolute pore size 1 micron or less, or tested and certified by National Safety Foundation (NSF) Standard 53 or 58 for cyst removal.

Solar Irradiation is a promising method but the Centre for Disease Control (CDC) does not comment on effectiveness for parasites. There are emerging studies that do report effectiveness.