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The standard method for diagnosing active infection is by finding the microfilariae via microscopic examination. This may be difficult, as in most parts of the world, microfilariae only circulate in the blood at night. For this reason, the blood has to be collected nocturnally. The blood sample is typically in the form of a thick smear and stained with Giemsa stain. Testing the blood serum for antibodies against the disease may also be used.
Identification of microfilariae by microscopic examination is a practical diagnostic procedure. Examination of blood samples will allow identification of microfilariae of "Loa loa". It is important to time the blood collection with the known periodicity of the microfilariae (between 10 am and 2 pm). The blood sample can be a thick smear, stained with Giemsa or haematoxylin and eosin (see staining). For increased sensitivity, concentration techniques can be used. These include centrifugation of the blood sample lyzed in 2% formalin (Knott's technique), or filtration through a Nucleopore membrane.
Antigen detection using an immunoassay for circulating filarial antigens constitutes a useful diagnostic approach, because microfilaremia can be low and variable. Interestingly, the Institute for Tropical Medicine reports that no serologic diagnostics are available. While this was once true, and many of recently developed methods of Antibody detection are of limited value—because substantial antigenic cross reactivity exists between filaria and other parasitic worms (helminths), and a positive serologic test does not necessarily distinguish between infections—up and coming serologic tests that are highly specific to "Loa loa" were furthered in 2008. They have not gone point-of-care yet, but show promise for highlighting high-risk areas and individuals with co-endemic loiasis and onchocerciasis. Specifically, Dr. Thomas Nutman and colleagues at the National Institutes of Health have described the a luciferase immunoprecipitation assay (LIPS) and the related QLIPS (quick version). Whereas a previously described LISXP-1 ELISA test had a poor sensitivity (55%), the QLIPS test is both practical, as it requires only a 15 minutes incubation, and has high sensitivity and specificity (97% and 100%, respectively). No report on the distribution status of LIPS or QLIPS testing is available, but these tests would help to limit complications derived from mass ivermectin treatment for onchocerciasis or dangerous strong doses of diethylcarbamazine for loiasis alone (as pertains to individual with high "Loa loa" microfilarial loads).
Physically, Calabar swellings (see image; needs image) are the primary tool for diagnosis. Identification of adult worms is possible from tissue samples collected during subcutaneous biopsies. Adult worms migrating across the eye are another potential diagnostic, but the short timeframe for the worm's passage through the conjunctiva makes this observation less common.
In the past, health care providers use a provocative injection of "Dirofilaria immitis" as a skin test antigen for filariasis diagnosis. If the patient was infected, the extract would cause an artificial allergic reaction and associated Calabar swelling similar to that caused, in theory, by metabolic products of the worm or dead worms.
Blood tests to reveal microfilaremia are useful in many, but not all cases, as one third of loiasis patients are amicrofilaremic. By contrast, eosinophilia is almost guaranteed in cases of loiasis, and blood testing for eosinophil fraction may be useful.
Various concentration methods are applied: membrane filter, Knott's concentration method, and sedimentation technique.
Polymerase chain reaction (PCR) and antigenic assays, which detect circulating filarial antigens, are also available for making the diagnosis. The latter are particularly useful in amicrofilaraemic cases. Spot tests for antigen are far more sensitive, and allow the test to be done anytime, rather in the late hours.
Lymph node aspirate and chylous fluid may also yield microfilariae. Medical imaging, such as CT or MRI, may reveal "filarial dance sign" in the chylous fluid; X-ray tests can show calcified adult worms in lymphatics. The DEC provocation test is performed to obtain satisfying numbers of parasites in daytime samples. Xenodiagnosis is now obsolete, and eosinophilia is a nonspecific primary sign.
A blood smear is a simple and fairly accurate diagnostic tool, provided the blood sample is taken during the period in the day when the juveniles are in the peripheral circulation. Technicians analyzing the blood smear must be able to distinguish between "W. bancrofti" and other parasites potentially present.
A polymerase chain reaction test can also be performed to detect a minute fraction, as little as 1 pg, of filarial DNA.
Some infected people do not have microfilariae in their blood. As a result, tests aimed to detect antigens from adult worms can be used.
Ultrasonography can also be used to detect the movements and noises caused by the movement of adult worms.
Dead, calcified worms can be detected by X-ray examinations.
Tender or enlarged inguinal lymph nodes or swelling in the extremities can alert physicians or public health officials to infection.
With appropriate laboratory equipment, microscopic examination of differential morphological features of microfilariae in stained blood films can aid diagnosis—in particular the examination of the tail portion, the presence of a sheath, and the size of the cephalic space. Giemsa staining will uniquely stain "B. malayi" sheath pink. However, blood films can prove difficult given the nocturnal periodicity of some forms of "B. malayi".
PCR based assays are highly sensitive and can be used to monitor infections both in the human and the mosquito vector. However, PCR assays are time-consuming, labor-intensive and require laboratory equipment. Lymphatic filariasis mainly affects the poor, who live in areas without such resources.
The ICT antigen card test is widely used in the diagnosis of "W. bancrofti", but commercial antigens of "B. malayi" have not been historically widely available. However, new research developments have identified a recombinant antigen (BmR1) that is both specific and sensitive in the detection of IgG4 antibodies against "B. malayi" and "B. timori" in ELISA and immunochromatographic rapid dipstick (Brugia Rapid) test. However, it appears that immunoreactivity to this antigen is variable in individuals infected with other filarial nematodes. This research has led to the development of two new rapid immunochromatographic IgG4 cassette tests – WB rapid and panLF rapid – which detect bancroftian filariasis and all three species of lymphatic filariasis, respectively, with high sensitivity and selectivity.
Filariasis is usually diagnosed by identifying microfilariae on Giemsa stained, thin and thick blood film smears, using the "gold standard" known as the finger prick test. The finger prick test draws blood from the capillaries of the finger tip; larger veins can be used for blood extraction, but strict windows of the time of day must be observed. Blood must be drawn at appropriate times, which reflect the feeding activities of the vector insects. Examples are "W. bancrofti", whose vector is a mosquito; night is the preferred time for blood collection. "Loa loa's" vector is the deer fly; daytime collection is preferred. This method of diagnosis is only relevant to microfilariae that use the blood as transport from the lungs to the skin. Some filarial worms, such as "M. streptocerca" and "O. volvulus", produce microfilarae that do not use the blood; they reside in the skin only. For these worms, diagnosis relies upon skin snips and can be carried out at any time.
The World Health Organization recommends mass deworming—treating entire groups of people who are at risk with a single annual dose of two medicines, namely albendazole in combination with either ivermectin or diethylcarbamazine citrate. With consistent treatment, since the disease needs a human host, the reduction of microfilariae means the disease will not be transmitted, the adult worms will die out, and the cycle will be broken. In sub-Saharan Africa, albendazole (donated by GlaxoSmithKline) is being used with ivermectin (donated by Merck & Co.) to treat the disease, whereas elsewhere in the world, albendazole is used with diethylcarbamazine. Transmission of the infection can be broken when a single dose of these combined oral medicines is consistently maintained annually for a duration of four to six years. Using a combination of treatments better reduces the number of microfilariae in blood. Avoiding mosquito bites, such as by using insecticide-treated mosquito bed nets, also reduces the transmission of lymphatic filariasis.
The Carter Center's International Task Force for Disease Eradication declared lymphatic filariasis one of six potentially eradicable diseases. According to medical experts, the worldwide effort to eliminate lymphatic filariasis is on track to potentially succeed by 2020.
For similar-looking but causally unrelated podoconiosis, international awareness of the disease will have to increase before elimination is possible. In 2011, podoconiosis was added to the World Health Organization's Neglected Tropical Diseases list, which was an important milestone in raising global awareness of the condition.
The efforts of the Global Programme to Eliminate LF are estimated to have prevented 6.6 million new filariasis cases from developing in children between 2000 and 2007, and to have stopped the progression of the disease in another 9.5 million people who had already contracted it. Dr. Mwele Malecela, who chairs the programme, said: "We are on track to accomplish our goal of elimination by 2020." In 2010, the WHO published a detailed progress report on the elimination campaign in which they assert that of the 81 countries with endemic LF, 53 have implemented mass drug administration, and 37 have completed five or more rounds in some areas, though urban areas remain problematic.
Diethylcarbamazine has been shown as an effective prophylaxis for "Loa loa" infection.
A study of Peace Corps volunteers in the highly Loa—endemic Gabon, for example, had the following results: 6 of 20 individuals in a placebo group contracted the disease, compared to 0 of 16 in the DEC-treated group. Seropositivity for antifilarial IgG antibody was also much higher in the placebo group. The recommended prophylactic dose is 300 mg DEC given orally once weekly. The only associated symptom in the Peace Corps study was nausea.
Researchers believe that geo-mapping of appropriate habitat and human settlement patterns may, with the use of predictor variables such as forest, land cover, rainfall, temperature, and soil type, allow for estimation of Loa loa transmission in the absence of point-of-care diagnostic tests. In addition to geo-mapping and chemoprophylaxis, the same preventative strategies used for malaria should be undertaken to avoid contraction of loiasis. Specifically, DEET-containing insect repellent, permethrin-soaked clothing, and thick, long-sleeved and long-legged clothing ought to be worn to decrease susceptibility to the bite of the mango or deer fly vector. Because the vector is day-biting, mosquito (bed) nets do not increase protection against loiasis.
Vector elimination strategies are an interesting consideration. It has been shown that the "Chrysops" vector has a limited flying range, but vector elimination efforts are not common, likely because the insects bite outdoors and have a diverse, if not long, range, living in the forest and biting in the open, as mentioned in the vector section.
No vaccine has been developed for loiasis and there is little report on this possibility.
Examination of blood samples will allow identification of microfilariae of "M. perstans", and "M. ozzardi" based. This diagnosis can be made on the basis of the morphology of the nuclei distribution in the tails of the microfilariae. The blood sample can be a thick smear, stained with Giemsa or hematoxylin and eosin. For increased sensitivity, concentration techniques can be used. These include centrifugation of the blood sample lyzed in 2% formalin (Knott's technique), or filtration through a Nucleopore membrane.
Examination of skin snips will identify microfilariae of "Onchocerca volvulus" and "M. streptocerca". Skin snips can be obtained using a corneal-scleral punch, or more simply a scalpel and needle. It is important that the sample be allowed to incubate for 30 minutes to 2 hours in saline or culture medium and then examined. This allows for the microfilariae that would have been in the tissue to migrate to the liquid phase of the specimen. Additionally, to differentiate the skin-dwelling filariae "M. streptocerca" and "Onchocerca volvulus", a nested polymerase chain reaction (PCR) assay was developed using small amounts of parasite material present in skin biopsies.
Prevention focuses on protecting against mosquito bites in endemic regions. Insect repellents and mosquito nets are useful to protect against mosquito bites. Public education efforts must also be made within the endemic areas of the world to successfully lower the prevalence of "W. bancrofti" infections.
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.
The Global Alliance to Eliminate Lymphatic Filariasis was launched by the World Health Organization in 2000 with two primary goals: 1) to interrupt transmission and 2) to alleviate the suffering of affected individuals. Mass drug treatment programs are the main strategy for interrupting parasite transmission, and morbidity management, focusing on hygiene, improves the quality of life of infected individuals.
Various control programs aim to stop onchocerciasis from being a public health problem. The first was the Onchocerciasis Control Programme (OCP), which was launched in 1974, and at its peak, covered 30 million people in 11 countries. Through the use of larvicide spraying of fast-flowing rivers to control black fly populations, and from 1988 onwards, the use of ivermectin to treat infected people, the OCP eliminated onchocerciasis as a public health problem. The OCP, a joint effort of the World Health Organisation, the World Bank, the United Nations Development Programme, and the UN Food and Agriculture Organization, was considered to be a success, and came to an end in 2002. Continued monitoring ensures onchocerciasis cannot reinvade the area of the OCP.
In 1995, the African Programme for Onchocerciasis Control began covering another 19 countries, mainly relying upon the use of ivermectin. Its goal is to set up a community-directed supply of ivermectin for those who are infected. In these ways, transmission has declined. In 2015, WHO was facilitating launch of an elimination program in Yemen.
In 1992, the Onchocerciasis Elimination Programme for the Americas, which also relies on ivermectin, was launched. On July 29, 2013, the Pan American Health Organization (PAHO) announced that after 16 years of efforts, Colombia had become the first country in the world to eliminate the parasitic disease onchocerciasis. In September 2015, the Onchocerciasis Elimination Program for the Americas announced that onchocerciasis only remained in a remote region on the border of Brazil and Venezuela. The area is home to the Yanomami indigenous people. The first countries to receive verification of elimination were Colombia in 2013, Ecuador in 2014, and Mexico in 2015. Guatemala has submitted a request for verification. The key factor in elimination is mass administration of the antiparasitic drug ivermectin. The initial projection was that the disease would be eliminated from remaining foci in the Americas by 2012.
No vaccine to prevent onchocerciasis infection in humans is available. A vaccine to prevent onchocerciasis infection for cattle is in phase three trials. Cattle injected with a modified and weakened form of "O. ochengi" larvae have developed very high levels of protection against infection. The findings suggest that it could be possible to develop a vaccine that protects people against river blindness using a similar approach. Unfortunately, a vaccine to protect humans is still many years off.
For the treatment of individuals, doxycycline is used to kill the "Wolbachia" bacteria that live in adult worms. This adjunct therapy has been shown to significantly lower microfilarial loads in the host, and may kill the adult worms, due to the symbiotic relationship between "Wolbachia" and the worm. In four separate trials over 10 years with various dosing regimens of doxycycline for individualized treatment, doxycycline was found to be effective in sterilizing the female worms and reducing their numbers over a period of four to six weeks. Research on other antibiotics, such as rifampicin, has shown it to be effective in animal models at reducing "Wolbachia" both as an alternative and as an adjunct to doxycycline. However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.
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.
Prevention can be partially achieved through limiting contact with vectors through the use of DEET and other repellents, but due to the predominantly relatively mild symptoms and the infection being generally asymptomatic, little has formally been done to control the disease.
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.
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.
Anthelmintics such as diethylcarbamazine and albendazole have shown promise in the treatment of "Brugia timori" filariasis. Some researchers are confident that "Brugia timori" filariasis may be an eradicable disease. Related filarial nematodes have been found highly sensitive to elimination of their endosymbiotic Wolbachia bacteria, and this may be a powerful attack route against "Brugia timori" as well.
Generally speaking, acanthocheilonemiasis does not show initial symptoms. However, if symptoms do arise, it is typically in individuals who are visiting highly infected areas rather than natives to those areas. A major common laboratory finding is an increase in specialized white blood cells, which is called eosinophilia.
Other symptoms include itchy skin, neurological symptoms, abdominal and chest pain, muscle pain, and swelling underneath the skin. If there are abnormally high levels of white blood cells, then a physical examination will most likely find an enlarged spleen or liver.
In certain scenarios, nematodes may physically lodge into the chest or abdomen, resulting in an inflammation. Diagnosis of this condition usually occurs via a blood smear examination under light microscopy.
Brugia timori is a human filarial parasitic nematode (roundworm) which causes the disease "Timor filariasis." While this disease was first described in 1965, the identity of "Brugia timori" as the causative agent was not known until 1977. In that same year, "Anopheles barbirostris" was shown to be its primary vector. There is no known animal reservoir host.
The standard of care is administration of antifilarial drugs, most commonly Ivermectin or diethyl-carbamazine (DEC). The most efficacious dose in all nematode and parasitic infections is 200 µg/kg of ivermectin. There has also been other various anthelminthic drugs used, such as mebendazole, levamisole, albendazole and thiabendazole. In worst-case scenarios, surgery may be necessary to remove nematodes from the abdomen or chest. However, mild cases usually do not require treatment.
Some of the strategies for controlling tropical diseases include:
- Draining wetlands to reduce populations of insects and other vectors, or introducing natural predators of the vectors.
- The application of insecticides and/or insect repellents) to strategic surfaces such as clothing, skin, buildings, insect habitats, and bed nets.
- The use of a mosquito net over a bed (also known as a "bed net") to reduce nighttime transmission, since certain species of tropical mosquitoes feed mainly at night.
- Use of water wells, and/or water filtration, water filters, or water treatment with water tablets to produce drinking water free of parasites.
- Sanitation to prevent transmission through human waste.
- In situations where vectors (such as mosquitoes) have become more numerous as a result of human activity, a careful investigation can provide clues: for example, open dumps can contain stagnant water that encourage disease vectors to breed. Eliminating these dumps can address the problem. An education campaign can yield significant benefits at low cost.
- Development and use of vaccines to promote disease immunity.
- Pharmacologic pre-exposure prophylaxis (to prevent disease before exposure to the environment and/or vector).
- Pharmacologic post-exposure prophylaxis (to prevent disease after exposure to the environment and/or vector).
- Pharmacologic treatment (to treat disease after infection or infestation).
- Assisting with economic development in endemic regions. For example, by providing microloans to enable investments in more efficient and productive agriculture. This in turn can help subsistence farming to become more profitable, and these profits can be used by local populations for disease prevention and treatment, with the added benefit of reducing the poverty rate.
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The diagnostic criteria for tropical pulmonary eosinophilia include:
- a history supportive of exposure to lymphatic filariasis;
- a peripheral eosinophilia count greater than 3 × 10/L);
- an elevated serum IgE levels (> 1000 kU/L);
- increased titers of antifilarial antibodies;
- peripheral blood negative for microfilariae; and
- a clinical response to diethylcarbamazine.
High antifilarial IgG titers to microfilariae often result in cross reactivity with other nonfilarial helminth antigens, such as strongyloides and schistosoma antigens, as demonstrated in reported cases. It is important to exclude other parasitic infections before tropical pulmonary eosinophilia is diagnosed, by serological tests, examination of stool specimens in a laboratory experienced in parasitic infections, or a trial of anthelminthic medication. Other parasitic infections, such as the zoonotic filariae, dirofilariasis, ascariasis, strongyloides, visceral larva migrans and hookworm disease, may also be confused with tropical pulmonary eosinophilia because of overlapping clinical features, serological profile and response to diethylcarbamazine. Radiological findings are nonspecific, with normal appearance on chest X-ray in up to 20% of patients. Lung biopsy is not part of the routine diagnostic workup of tropical pulmonary eosinophilia.
Owing to the non-specific nature of the presentation of symptoms, diagnosis of malaria in non-endemic areas requires a high degree of suspicion, which might be elicited by any of the following: recent travel history, enlarged spleen, fever, low number of platelets in the blood, and higher-than-normal levels of bilirubin in the blood combined with a normal level of white blood cells. Reports in 2016 and 2017 from countries were malaria is common suggest high levels of over diagnosis due to insufficient or inaccurate laboratory testing.
Malaria is usually confirmed by the microscopic examination of blood films or by antigen-based rapid diagnostic tests (RDT). In some areas, RDTs need to be able to distinguish whether the malaria symptoms are caused by "Plasmodium falciparum" or by other species of parasites since treatment strategies could differ for non-"P. falciparum" infections. Microscopy is the most commonly used method to detect the malarial parasite—about 165 million blood films were examined for malaria in 2010. Despite its widespread usage, diagnosis by microscopy suffers from two main drawbacks: many settings (especially rural) are not equipped to perform the test, and the accuracy of the results depends on both the skill of the person examining the blood film and the levels of the parasite in the blood. The sensitivity of blood films ranges from 75–90% in optimum conditions, to as low as 50%. Commercially available RDTs are often more accurate than blood films at predicting the presence of malaria parasites, but they are widely variable in diagnostic sensitivity and specificity depending on manufacturer, and are unable to tell how many parasites are present.
In regions where laboratory tests are readily available, malaria should be suspected, and tested for, in any unwell person who has been in an area where malaria is endemic. In areas that cannot afford laboratory diagnostic tests, it has become common to use only a history of fever as the indication to treat for malaria—thus the common teaching "fever equals malaria unless proven otherwise". A drawback of this practice is overdiagnosis of malaria and mismanagement of non-malarial fever, which wastes limited resources, erodes confidence in the health care system, and contributes to drug resistance. Although polymerase chain reaction-based tests have been developed, they are not widely used in areas where malaria is common as of 2012, due to their complexity.