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Specific helminths can be identified through microscopic examination of their eggs (ova) found in faecal samples. The number of eggs is measured in units of eggs per gram. However, it does not quantify mixed infections, and in practice, is inaccurate for quantifying the eggs of schistosomes and soil-transmitted helmiths. Sophisticated tests such as serological assays, antigen tests, and molecular diagnosis are also available; however, they are time-consuming, expensive and not always reliable.
A stool ova and parasites exam reveals the presence of typical whipworm eggs. Typically, the Kato-Katz thick-smear technique is used for identification of the "Trichuris trichiura" eggs in the stool sample.
Although colonoscopy is not typically used for diagnosis, as the adult worms can be overlooked, especially with imperfect colon, there have been reported cases in which colonoscopy has revealed adult worms. Colonoscopy can directly diagnose trichuriasis by identification of the threadlike form of worms with an attenuated, whip-like end. Colonoscopy has been shown to be a useful diagnostic tool, especially in patients infected with only a few male worms and with no eggs presenting in the stool sample.
Trichuriasis can be diagnosed when "T. trichiura" eggs are detected in stool examination. Eggs will appear barrel-shaped and unembryonated, having bipolar plugs and a smooth shell. Rectal prolapse can be diagnosed easily using defecating proctogram and is one of many methods for imaging the parasitic infection. Sigmoidoscopys show characteristic white bodies of adult worms hanging from inflamed mucosa ("coconut cake rectum").
For basic diagnosis, specific helminths can be generally identified from the faeces, and their eggs microscopically examined and enumerated using fecal egg count method. However, there are certain limitations such as the inability to identify mixed infections, and on clinical practice, the technique is inaccurate and unreliable.
A novel effective method for egg analysis is the Kato-Katz technique. It is a highly accurate and rapid method for "A. lumbricoides" and "T. trichiura"; however not so much for hookworm, which could be due to fast degeneration of the rather delicate hookworm eggs.
The standard method for diagnosing necatoriasis is through identification of "N. americanus" eggs in a fecal sample using a microscope. Eggs can be difficult to visualize in a lightly infected sample so a concentration method is generally used such as flotation or sedimentation. However, the eggs of "A. duodenale" and "N. americanus" cannot be distinguished; thus, the larvae must be examined to identify these hookworms. Larvae cannot be found in stool specimens unless the specimen was left at ambient temperature for a day or more.
The most common technique used to diagnose a hookworm infection is to take a stool sample, fix it in 10% formalin, concentrate it using the formalin-ethyl acetate sedimentation technique, and then create a wet mount of the sediment for viewing under a microscope.
Limited access to essential medicine poses a challenge to the eradication of trichuriasis worldwide. Also, it is a public health concern that rates of post-treatment re-infection need to be determined and addressed to diminish the incidence of untreated re-infection. Lastly, with mass drug administration strategies and improved diagnosis and prompt treatment, detection of an emergence of antihelminthic drug resistance should be examined.
Mass Drug Administration (preventative chemotherapy) has had a positive effect on the disease burden of trichuriasis in East and West Africa, especially among children, who are at highest risk for infection.
In patients with elevated eosiniphils, serology can be used to confirm a diagnosis of Angiostrongylias rather than infection with another parasite. There are a number of immunoassays that can aid in diagnosis, however serologic testing is available in few labs in the endemic area, and is frequently too non-specific. Some cross reactivity has been reported between "A. cantonensis" and trichinosis, making diagnosis less specific.
The most definitive diagnosis always arises from the identification of larvae found in the CSF or eye, however due to this rarity a clinical diagnosis based on the above tests is most likely.
Diagnosis depends on finding characteristic worm eggs on microscopic examination of the stools, although this is not possible in early infection. Early signs of infection in most dogs include limbular limping and anal itching. The eggs are oval or elliptical, measuring 60 µm by 40 µm, colorless, not bile stained and with a thin transparent hyaline shell membrane. When released by the worm in the intestine, the egg contains an unsegmented ovum. During its passage down the intestine, the ovum develops and thus the eggs passed in feces have a segmented ovum, usually with 4 to 8 blastomeres.
As the eggs of both "Ancylostoma" and "Necator" (and most other hookworm species) are indistinguishable, to identify the genus, they must be cultured in the lab to allow larvae to hatch out. If the fecal sample is left for a day or more under tropical conditions, the larvae will have hatched out, so eggs might no longer be evident. In such a case, it is essential to distinguish hookworms from "Strongyloides" larvae, as infection with the latter has more serious implications and requires different management. The larvae of the two hookworm species can also be distinguished microscopically, although this would not be done routinely, but usually for research purposes. Adult worms are rarely seen (except via endoscopy, surgery or autopsy), but if found, would allow definitive identification of the species. Classification can be performed based on the length of the buccal cavity, the space between the oral opening and the esophagus: hookworm rhabditoform larvae have long buccal cavities whereas "Strongyloides" rhabditoform larvae have short buccal cavities.
Recent research has focused on the development of DNA-based tools for diagnosis of infection, specific identification of hookworm, and analysis of genetic variability within hookworm populations. Because hookworm eggs are often indistinguishable from other parasitic eggs, PCR assays could serve as a molecular approach for accurate diagnosis of hookworm in the feces.
Brain lesions, with invasion of both gray and white matter, can be seen on a CT or MRI. However MRI findings tend to be inconclusive, and usually include nonspecific lesions and ventricular enlargement. Sometimes a hemorrhage, probably produced by migrating worms, is present and of diagnostic value.
Prevention and control measures to prevent soil-transmitted helminthiasis are the following: availability of clean water for personal and domestic uses, improved access to sanitation which includes the use of properly functioning and clean toilets by all community members, education on personal hygiene such as hand washing and hygienic and safe food preparation; eliminating the use of untreated human faeces as fertilizer.
In regions where helminthiasis is common, mass deworming treatments may be performed, particularly among school-age children, who are a high-risk group. Most of these initiatives are undertaken by the World Health Organization (WHO) with positive outcomes in many regions. Deworming programs can improve school attendance by 25 percent. Although deworming improves the health of an individual, outcomes from mass deworming campaigns, such as reduced deaths or increases in cognitive ability, nutritional benefits, physical growth, and performance, are uncertain or not apparent.
Evaluation of numerous public health interventions has generally shown that improvement in each individual component ordinarily attributed to poverty (for example, sanitation, health education and underlying nutrition status) often have minimal impact on transmission. For example, one study found that the introduction of latrines into a resource-limited community only reduced the prevalence of hookworm infection by four percent. However, another study in Salvador, Brazil found that improved drainage and sewerage had a significant impact (p<0.0001) on the prevalence of hookworm infection but no impact at all on the intensity of hookworm infection. This seems to suggest that environmental control alone has a limited but incomplete effect on the transmission of hookworms. It is imperative, therefore, that more research is performed to understand the efficacy and sustainability of integrated programs that combine numerous preventive methods including education, sanitation, and treatment.
Education, improved sanitation, and controlled disposal of human feces are critical for prevention. Nonetheless, wearing shoes in endemic areas helps reduce the prevalence of infection.
The clinical aspects of ancylostomiasis were first described in Europe as "miner's anaemia". During the construction of the Gotthard Tunnel in Switzerland (1871–1881), a large number of miners suffered from severe anaemia of unknown cause. Medical investigations let to the understanding that it was caused by "Ancylostoma duodenale" (favoured by high temperatures and humidity) and to "major advances in parasitology, by way of research into the aetiology, epidemiology and treatment of ancylostomiasis".
Hookworms still account for high proportion of debilitating disease in the tropics and 50-60,000 deaths per year can be attributed to this disease.
Control of this parasite should be directed against reducing the level of
environmental contamination. Treatment of heavily infected individuals is one
way to reduce the source of contamination (one study has estimated that 60% of
the total worm burden resides in less than 10% of the population). Other
obvious methods are to improve access to sanitation, e.g. toilets, but also
convincing people to maintaining them in a clean, functional state, thereby making
them conducive to use.
Under most situations, infection is hard to recognize because the symptoms are mild or even absent. In humans and wild animals, infection is not easily identified. Especially the adult flukes, even if in large number, generally do not cause complications. There is not yet a standard diagnostic test. Therefore, manual diagnosis is done at many levels. Diagnosis basically relies on a combination of postmortem analyses, clinical signs displayed by the animals, and response to drenching. In heavy infection, symptoms are easily observed in sheep and cattle as they become severely anorexic or inefficiently digest food, and become unthrifty. Copious fetid diarrhea is an obvious indication, as the soiling of hind legs and tails with fluid feces are readily noticeable. Even though it not always the case, immature flukes can be identified from the fluid excrement. On rare occasions, eggs can be identified from stools of suspected animals. In developing countries diagnosis and prognosis is often hindered by multiple infections with other trematodes, such as "Fasciola hepatica" and schistosomes, because these flukes are given primary importance due to their pervasive nature.
The following diagnostic methods are not routinely available to patients. Researchers have reported that they are more reliable at detecting infection, and in some cases can provide the physician with information to help determine whether "Blastocystis" infection is the cause of the patient's symptoms:
Serum antibody testing: A 1993 research study performed by the NIH with United States patients suggested that it was possible to distinguish symptomatic and asymptomatic infection with "Blastocystis" using serum antibody testing. The study used blood samples to measure the patient's immune reaction to chemicals present on the surface of the "Blastocystis" cell. It found that patients diagnosed with symptomatic "Blastocystis" infection exhibited a much higher immune response than controls who had "Blastocystis" infection but no symptoms. The study was repeated in 2003 at Ain Shams University in Egypt with Egyptian patients with equivalent results.
Fecal antibody testing: A 2003 study at Ain Shams University in Egypt indicated that patients symptomatically infected could be distinguished with a fecal antibody test. The study compared patients diagnosed with symptomatic "Blastocystis" infection to controls who had "Blastocystis" infection but no symptoms. In the group with symptoms, IgA antibodies to "Blastocystis" were detected in fecal specimens that were not present in the healthy control group.
Stool culture: Culturing has been shown to be a more reliable method of identifying infection. In 2006, researchers reported the ability to distinguish between disease causing and non-disease causing isolates of "Blastocystis" using stool culture. "Blastocystis" cultured from patients who were sick and diagnosed with "Blastocystis" infection produced large, highly adhesive amoeboid forms in culture. These cells were absent in "Blastocystis" cultures from healthy controls. Subsequent genetic analysis showed the "Blastocystis" from healthy controls was genetically distinct from that found in patients with symptoms. Protozoal culture is unavailable in most countries due to the cost and lack of trained staff able to perform protozoal culture.
Genetic analysis of isolates: Researchers have used techniques which allow the DNA of "Blastocystis" to be isolated from fecal specimens. This method has been reported to be more reliable at detecting "Blastocystis" in symptomatic patients than stool culture. This method also allows the species group of "Blastocystis" to be identified. Research is continuing into which species groups are associated with symptomatic (see Genetics and Symptoms) blastocystosis.
Immuno-fluorescence (IFA) stain: An IFA stain causes "Blastocystis" cells to glow when viewed under a microscope, making the diagnostic method more reliable. IFA stains are in use for Giardia and Cryptosporidium for both diagnostic purposes and water quality testing. A 1991 paper from the NIH described the laboratory development of one such stain. However, no company currently offers this stain commercially.
Anecdotal data gathered from helminth self-treaters and their physicians and presented in socio-medical studies suggest that a much larger number of diseases may be amenable to helminthic therapy than are currently being investigated by formal clinical trials.
Amphistomiasis is considered a neglected tropical disease, with no prescription drug for treatment and control. Therefore, management of infestation is based mainly on control of the snail population, which transmit the infective larvae of the flukes. However, there are now drugs shown to be effective including resorantel, oxyclozanide, clorsulon, ivermectin, niclosamide, bithional and levamisole. An in vitro demonstration shows that plumbagin exhibits high efficacy on adult flukes. Since the juvenile flukes are the causative individuals of the disease, effective treatment means control of the immature fluke population. Prophylaxis is therefore based on disruption of the environment (such as proper drainage) where the carrier snails inhabit, or more drastic action of using molluscicides to eradicate the entire population. For treatment of the infection, drugs effective against the immature flukes are recommended for drenching. For this reason oxyclozanide is advocated as the drug of choice. It effectively kills the flukes within a few hours and it effective against the flukes resistant to other drugs. The commercially prescribed dosage is 5 mg/kg body weight or 18.7 mg/kg body weight in two divided dose within 72 hours. Niclosamide is also extensively used in mass drenching of sheep. Successfully treated sheep regain appetite within a week, diarrhoea stops in about three days, and physiological indicators (such as plasma protein and albumin levels) return to normal in a month.
Diagnosis is usually performed by submitting multiple stool samples for examination by a parasitologist in a procedure known as an ova and parasite examination. About 30% of children with "D. fragilis" infection exhibit peripheral blood eosinophilia.
A minimum of three stool specimens having been immediately fixed in polyvinyl alcohol fixative, sodium acetate-acetic acid-formalin fixative, or Schaudinn's fixative should be submitted, as the protozoan does not remain morphologically identifiable for long. All specimens, regardless of consistency, are permanently stained prior to microscopic examination with an oil immersion lens. The disease may remain cryptic due to the lack of a cyst stage if these recommendations are not followed.
The trophozoite forms have been recovered from formed stool, thus the need to perform the ova and parasite examination on specimens other than liquid or soft stools. DNA fragment analysis provides excellent sensitivity and specificity when compared to microscopy for the detection of "D. fragilis" and both methods should be employed in laboratories with PCR capability. The most sensitive detection method is parasite culture, and the culture medium requires the addition of rice starch.
An indirect fluorescent antibody (IFA) for fixed stool specimens has been developed.
1. One researcher investigated the phenomenon of symptomatic relapse following treatment of infection with "D. fragilis" in association with its apparent disappearance from stool samples. The organism could still be detected in patients through colonoscopy or by examining stool samples taken in conjunction with a saline laxative.
2. A study found that trichrome staining, a traditional method for identification, had a sensitivity of 36% (9/25) when compared to stool culture.
3. An additional study found that the sensitivity of staining was 50% (2/4), and that the organism could be successfully cultured in stool specimens up to 12-hours old that were kept at room temperature.
Diagnosis is performed by determining if the infection is present, and then making a decision as to whether the infection is responsible for the symptoms. Diagnostic methods in clinical use have been reported to be of poor quality and more reliable methods have been reported in research papers.
For identification of infection, the only method clinically available in most areas is the "Ova and Parasite" (O&P) exam, which identifies the presence of the organism by microscopic examination of a chemically preserved stool specimen. This method is sometimes called "Direct Microscopy". In the United States, pathologists are required to report the presence of "Blastocystis" when found during an O&P exam, so a special test does not have to be ordered. Direct Microscopy is inexpensive, as the same test can identify a variety of gastrointestinal infections, such as "Giardia", "Entamoeba histolytica", "Cryptosporidium". However one laboratory director noted that pathologists using conventional microscopes failed to identify many "Blastocystis" infections, and indicated the necessity for special microscopic equipment for identification. The following table shows the sensitivity of Direct Microscopy in detecting "Blastocystis" when compared to stool culture, a more sensitive technique. Stool culture was considered by some researchers to be the most reliable technique, but a recent study found stool culture only detected 83% of individuals infected when compared to polymerase chain reaction (PCR) testing.
Reasons given for the failure of Direct Microscopy include: (1) Variable Shedding: The quantity of "Blastocystis" organisms varies substantially from day to day in infected humans and animals; (2) Appearance: Some forms of "Blastocystis" resemble fat cells or white blood cells, making it difficult to distinguish the organism from other cells in the stool sample; (3) Large number of morphological forms: "Blastocystis" cells can assume a variety of shapes, some have been described in detail only recently, so it is possible that additional forms exist but have not been identified.
Several methods have been cited in literature for determination of the significance of the finding of "Blastocystis":
1. Diagnosis only when large numbers of organism present: Some physicians consider "Blastocystis" infection to be a cause of illness only when large numbers are found in stool samples. Researchers have questioned this approach, noting that it is not used with any other protozoal infections, such as "Giardia" or "Entamoeba histolytica". Some researchers have reported no correlation between number of organisms present in stool samples and the level of symptoms. A study using polymerase chain reaction testing of stool samples suggested that symptomatic infection can exist even when sufficient quantities of the organism do not exist for identification through Direct Microscopy.
2. Diagnosis-by-exclusion: Some physicians diagnose "Blastocystis" infection by excluding all other causes, such as infection with other organisms, food intolerances, colon cancer, etc. This method can be time consuming and expensive, requiring many tests such as endoscopy and colonoscopy.
3. Disregarding "Blastocystis" : In the early to mid-1990s, some US physicians suggested all findings of "Blastocystis" are insignificant. No recent publications expressing this opinion could be found.
Biotechnology companies in the developing world have targeted neglected tropical diseases due to need to improve global health.
Mass drug administration is considered a possible method for eradication, especially for lymphatic filariasis, onchocerciasis, and trachoma, although drug resistance is a potential problem. According to Fenwick, Pfizer donated 70 million doses of drugs in 2011 to eliminate trachoma through the International Trachoma Initiative. Merck has helped The African Programme for the Control of Onchocerciasis (APOC) and Oncho Elimination Programme for the Americas to greatly diminished the effect of Onchocerciasis by donating ivermectin. Merck KGaA pledged to give 200 million tablets of praziquantel over 10 years, the only cure for schistosomiasis. GlaxoSmithKline has donated two billion tablets of medicine for lymphatic filariasis and pledged 400 million deworming tablets per year for five years in 2010. Johnson & Johnson has pledged 200 million deworming tablets per year. Novartis has pledged leprosy treatment, EISAI pledged two billion tablets to help treat lymphatic filariasis.
Inclusion of NTDs into initiatives for malaria, HIV/AIDS, and tuberculosis, as well as integration of NTD treatment programs, may have advantages given the strong link between these diseases and NTDs. Some neglected tropical diseases share common vectors (sandflies, black flies, and mosquitos). Both medicinal and vector control efforts may be combined.
A four-drug rapid-impact package has been proposed for widespread proliferation. Administration may be made more efficient by targeting multiple diseases at once, rather than separating treatment and adding work to community workers. This package is estimated to cost US$0.40 per patient. When compared to stand-alone treatment, the savings are estimated to be 26–47%. While more research must be done in order to understand how NTDs and other diseases interact in both the vector and the human stages, safety assessments have so far produced positive results.
Many neglected tropical diseases and other prevalent diseases share common vectors, creating another opportunity for treatment and control integration. One such example of this is malaria and lymphatic filariasis. Both diseases are transmitted by the same or related mosquito vectors. Vector control, through the distribution of insecticide treated nets, reduces the human contact with a wide variety of disease vectors. Integrated vector control may also alleviate pressure on mass drug administration, especially with respect to rapidly evolving drug resistance. Combining vector control and mass drug administration deemphasizes both, making each less susceptible to resistance evolution.
Evidence in support of the idea that helminthic infections reduce the severity of autoimmune diseases is primarily derived from animal models. Studies conducted on mice and rat models of colitis, muscular sclerosis, type 1 diabetes, and asthma have shown helminth-infected subjects to display protection from the disease. While helminths are often considered a homogenous group, considerable differences exist between species and the utilization of species in clinical research varies between human and animal trials. As such, caution must be exercised when interpreting the results from animal models.
Helminthic therapy is currently being studied as a treatment for several (non-viral) autoimmune diseases in humans including celiac disease, Crohn's disease, multiple sclerosis, ulcerative colitis, and atherosclerosis. It is currently unknown which clinical dose or species of helminth is the most effective method of treatment. Hookworms have been linked to reduced risk of developing asthma, while "Ascaris lumbricoides" (roundworm infection) was associated with an "increased" risk of asthma. Similarly, "Hymenolepis nana", "Trichoris trichiura", "Ascaris lumbricoides", "Strongyloides stercolaris", "Enterobius vermicularis", and "Trichuris suis" ova have all been found to lower the number of symptom exacerbations, reduce the number of symptom relapses, and decrease the number of new or enlarging brain lesions in patients with multiple sclerosis at doses ranging from 1,180 to 9,340 eggs per gram. However, "Ascaris lumbricoides", "Strongyloides stercolaris" and "Enterobius vermicularis" are not considered suitable for therapeutic use in humans because they do not meet the criteria for a therapeutic helminth.
"Trichuris suis" ova has been used in most cases to treat autoimmune disorders because it is thought to be non-pathogenic in humans and therefore has been rendered as safe.
The use of "Trichuris suis" ova has been granted by the USA Food and Drug Administration as an investigational medicinal product (IMP). While in the UK, the hookworm "Necator americanus" has been granted an IMP license by the Medicines and Healthcare Regulatory Authority. This hookworm is likely to be relatively safe, although it can cause temporary gastrointestinal side effects, especially following the initial inoculation and with larger doses.
The general ideal characteristics for a therapeutic helminth are as follows:
- Little or no pathogenic potential
- Does not multiply in the host
- Cannot be directly spread to close contacts
- Produces a self-limited colonization in humans
- Produces an asymptomatic colonization in humans
- Does not alter behaviour in patients with depressed immunity
- Is not affected by most commonly used medications
- Can be eradicated with an anti-helminthic drug
- Can be isolated free of other potential pathogens
- Can be isolated or produced in large numbers
- Can be made stable for transport and storage
- Easy to administer
Diagnosis of toxoplasmosis in humans is made by biological, serological, histological, or molecular methods, or by some combination of the above. Toxoplasmosis can be difficult to distinguish from primary central nervous system lymphoma. It mimics several other infectious diseases so clinical signs are non-specific and are not sufficiently characteristic for a definite diagnosis. As a result, the diagnosis is made by a trial of therapy (pyrimethamine, sulfadiazine, and folinic acid (USAN: leucovorin)), if the drugs produce no effect clinically and no improvement on repeat imaging.
"T. gondii" may also be detected in blood, amniotic fluid, or cerebrospinal fluid by using polymerase chain reaction. "T. gondii" may exist in a host as an inactive cyst that would likely evade detection.
Serological testing can detect "T. gondii" antibodies in blood serum, using methods including the Sabin–Feldman dye test (DT), the indirect hemagglutination assay, the indirect fluorescent antibody assay (IFA), the direct agglutination test, the latex agglutination test (LAT), the enzyme-linked immunosorbent assay (ELISA), and the immunosorbent agglutination assay test (IAAT).
The most commonly used tests to measure IgG antibody are the DT, the ELISA, the IFA, and the modified direct agglutination test. IgG antibodies usually appear within a week or two of infection, peak within one to two months, then decline at various rates. "Toxoplasma" IgG antibodies generally persist for life, and therefore may be present in the bloodstream as a result of either current or previous infection.
To some extent, acute toxoplasmosis infections can be differentiated from chronic infections using an IgG avidity test, which is a variation on the ELISA. In the first response to infection, toxoplasma-specific IgG has a low affinity for the toxoplasma antigen; in the following weeks and month, IgG affinity for the antigen increases. Based on the IgG avidity test, if the IgG in the infected individual has a high affinity, it means that the infection began three to five months before testing. This is particularly useful in congenital infection, where pregnancy status and gestational age at time of infection determines treatment.
In contrast to IgG, IgM antibodies can be used to detect acute infection, but generally not chronic infection. The IgM antibodies appear sooner after infection than the IgG antibodies and disappear faster than IgG antibodies after recovery. In most cases, "T. gondii"-specific IgM antibodies can first be detected approximately a week after acquiring primary infection, and decrease within one to six months; 25% of those infected are negative for "T. gondii"-specific IgM within seven months. However, IgM may be detectable months or years after infection, during the chronic phase, and false positives for acute infection are possible. The most commonly used tests for the measurement of IgM antibody are double-sandwich IgM-ELISA, the IFA test, and the immunosorbent agglutination assay (IgM-ISAGA). Commercial test kits often have low specificity, and the reported results are frequently misinterpreted.
One way to diagnose "C. felis" is by taking blood and performing a peripheral blood smear to look for the erythrocytic piroplasms. The erythrocytic piroplasms are usually shaped like signet rings and are 1 to 1.5 µm. Not all cats that are infected will have the piroplasms on their blood smear, especially if they are early in disease course. Another method of diagnosing infection in sick cats is to take needle aspirates of affected organs and find the schizonts inside mononuclear cells in the tissues; examination of tissue is also useful for the diagnosis after cats have died. Blood samples can be sent away for polymerase chain reaction (PCR) testing to confirm infection. Other diseases that might resemble cytauxzoonosis should be ruled out. A major rule-out for "C. felis" is "Mycoplasma haemofelis" (formerly known as "Haemobartonella felis"); clinical signs can be similar to cytauxzoonosis and the organism may be confused on the peripheral smear. Because it causes similar signs in outdoor cats during the spring and summer, tularemia is another disease the veterinarian may want to rule out.
Other laboratory tests are often abnormal in sick cats. The CBC of an infected cat often shows a pancytopenia, or a decrease in red blood cells, white blood cells, and platelets; in some cases there is not a decrease in all three values. Clotting tests may be prolonged. Increased liver enzymes are common, and electrolyte disturbances, hyperglycemia, and acid-base disturbances can also be observed.