MODE OF TRANSMISSION

The parasite is found on surfaces or in soil, food, or water that has been contaminated with feces from infected humans or animals. Infection is transmitted commonly through ingestion of infectious G lamblia cysts. In the intestine, excystation occurs and trophozoites are released into the feces. A summary of the transmission of the parasite is shown in Figure 1.

Giardia infrequently is transmitted sexually specifically through oral-anal practices. The incubation period is 3-35 days but 7-10 days on the average.

Figure 1.

Life Cycle of Giardia. Source- Centers for Disease Control and Prevention

CLINICAL PRESENTATION

The clinical manifestations include acute or chronic diarrheal disease, but the infection may be asymptomatic even in children. In a Nigeria Study (3) that evaluated stool samples of children aged between 0-5 years, about half-(41%) were positive for G. lamblia. The extraintestinal manifestations of Giardiasis include allergic presentations resulting from immune system activation, and long-term consequences such as ocular pathologies, arthritis, allergies, growth failure, muscular, and metabolic complications (4-5).

ENDOCRINE AND METABOLIC ABNORMALITIES

The complications relating to endocrine and metabolic dysfunction include growth failure and hypothyroidism. The Nigerian Report described above showed a positive association between asymptomatic giardiasis and malnutrition. The relation between Giardiasis and growth failure is explained mainly by malabsorption leading to protein energy malnutrition and micronutrient deficiencies. Other than nutritional status, other contributory factors to growth stunting in children include sanitary and socio-economic conditions, loss of intestinal surface area, and maldigestion (4-5).

Giardia infection has no direct effect or impact on thyroid function but has been reported to indirectly affect thyroid status. Worsening of hypothyroidism related to malabsorption of levothyroxine tablets occasioned by the presence of Giardia infection has been documented in the literature (6-7).

DIAGNOSIS AND MANAGEMENT

The diagnosis is made by demonstration of cysts or trophozoites in stool samples. Other means of diagnosis include small bowel biopsy and stool ELISA. The mainstay of treatment is metronidazole. Patients with stunted growth often experience catch- up growth following treatment of giardiasis.

MODE OF TRANSMISSION

Leishmania spp. is a parasite with a dimorphic life cycle that is controlled by the passage from vector to host .All three forms of Leishmaniasis are transmitted by the bite of infected female sand fly. The vector phase of the life cycle begins when the vector ingests blood containing the parasites with the parasites undergoing differentiation and ultimately becoming promastigotes and pass into the proboscis where where they can inoculate the host during feeding of the vector (8). These human and vector stages of Leishmania are shown in Figure 2. Infiltration of the reticuloendothelial system by amastigotes leads to the biochemical and clinical features of the disease.

Vertical transmission of visceral leishmaniasis may occur during pregnancy while cutaneous leishmaniasis may be transmitted through physical contact. Transmission via contaminated needles, blood transfusion, sexual intercourse and vertical transmission are modes of transmission that are documented albeit infrequently (8).

Figure 2.

Life cycle of Leishmania. Source -CDC

CLINICAL PRESENTATION

Visceral Leishmaniasis (VL) may present with fever, malnutrition, weight loss , hepatosplenomegaly and death if treatment is delayed or sub-optimal. Cutaneous Leishmaniasis presents with skin ulceration and nodules and the Mucocutaneous form of Leishmaniasis with skin and mucous involvement.

ENDOCRINE AND METABOLIC ABNORMALITIES

Evidence of involvement of several endocrine organs- pituitary, adrenal, thyroid, and sex glands- via histopathologic studies have been documented in VL (9). However abnormal endocrine function tests in some instances without clinical manifestations have been documented.

Reports from Africa and Europe show that thyroid function may be affected in VL but the abnormalities detected are most likely a result of euthyroid sick syndrome (ESS) or non-thyroidal illness (NTI) with no clinical presentation of thyroid disease (10-12). VL has been reported to present with primary adrenal insufficiency in with clinically overt features and in some cases biochemical evidence without clinical features may occur. Primary adrenal insufficiency (AI) was reported in VL in a patient without HIV infection and a patient with concomitant HIV infection and was attributable to parasitic infiltration of the organ (13-14). A Brazilian Series reported a prevalence rate of AI to be about 50% in persons with VL (12). In the Brazilian Report (12) that compared hormonal parameters between persons with chronic leishmaniasis and control subjects, the following were noted in some of the subjects with leishmaniasis; a) features of pituitary dysfunction characterized by low TSH, low T4, and low T3 levels (ESS/NTI), b) elevated ACTH with normal cortisol levels, c) high FSH, LH, and low testosterone levels. Other endocrine abnormalities include low parathyroid hormone (PTH) and decreased total and ionized calcium levels.

An unusual presentation of VL is adrenal cysts which has been reported to come to clinical attention because of the mass effect (15-16). The Syndrome of inappropriate ADH secretion (SIADH) is often reported in VL with hyponatremia documented as a significant contributory factor to mortality of the disease (17). The endocrine and metabolic abnormalities of Leishmaniasis and potential mechanisms underlying their occurrence are shown in Table 1.

DIAGNOSIS AND TREATMENT

A combination of clinical symptoms and laboratory parameters clinches the diagnosis. The laboratory tests involve the detection of the parasites in samples taken from the base of the ulcer and dermal scrapings- Wright ‘s stain detects round or ovoid parasite in the cytoplasm of macrophages.

Polymerase chain reaction for detection of the parasite in peripheral blood and bone marrow samples IS diagnostic. Other tests to support the diagnosis is the Leishman test, which essentially refers to observation of a delayed tuberculin type of reaction following an Intradermal injection of leishmanial antigen.

The mainstay of treatment is the pentavalent antimony compounds. Other pharmacotherapies include amphotericin B, oral miltefosine, pentamidine, and antibiotics. Treatment is individualized, thus persons with associated endocrine/metabolic dysfunction are treated on a case-by-case basis.

MODE OF TRANSMISSION

In HAT the tsesefly (glossina specie) injects metacyclic trypomastogotes into the skin and these pass into the blood stream and are subsequently carried to other parts of the body and body fluids. The tsetsefly becomes infected when it bites an infected person. Trypanosoma brucei gambiense may also be acquired congenitally from an infected mother.

Chagas disease is transmitted by a group of blood-feeding insects known as kissing bugs or triatomid bugs. The pathogen normally circulates between bugs and wild animals in sylvatic habitats; infected bugs in domestic habitats can transmit Chagas to humans and domestic animals (dogs, guinea pigs). Details of the life cycle and transmission of the pathogen is shown in Figure 4.

Figure 4.

Transmission of Chagas Disease

CLINICAL PRESENTATION

Trypanosomiasis may cause acute illness but on the other hand the infection may be asymptomatic. Chagas disease (CD) presents in three phases: acute, indeterminate, and chronic. The acute phase occurs immediately following infection and is usually asymptomatic in most people but when symptomatic, presentation is essentially those of malaise and skin lesions. The indeterminate phase is usually asymptomatic but may progress to a chronic phase where organ systems mainly the heart and sometimes the gastrointestinal tract are affected.

HAT is characterized by an early hyper-hemolytic phase in which the trypanosomes are restricted to the blood and the lymphatic system and also characterized by organomegaly and lymphadenopathy. This is followed by a late phase or the meningo-encephalitic stage characterized by neuro-psychiatric and endocrinal disorders.

ENDOCRINE AND METABOLIC ABNORMALITIES

These occur infrequently and includes systemic neuroendocrine manifestations in the sympathetic and parasympathetic ganglia. In HAT, documented endocrine abnormalities include adrenal insufficiency, hypothyroidism, and hypogonadism in the absence of autoantibodies (18). Some authors have reported thyroid dysfunction specifically hypothyroidism in untreated HAT (19).

Adrenal insufficiency in trypanosomiasis may be primary or secondary and this is seen especially in untreated cases (20). The adrenal may serve as a reservoir for the T. cruzi infection and some investigators have noted a correlation between Chagasic myocarditis and infection within the central vein of the adrenal gland (21).

Secondary hypogonadism in both sexes had also been demonstrated in some reports which clearly showed that in the majority of the cases, the pathology was not at the level of the pituitary gland but rather an extra pituitary origin (22). Clearly, primary hypogonadism was not demonstrated to be a contributory factor to cases of hypogonadism in persons with trypanosomiasis.

Metabolic abnormalities are infrequently reported however a case of spurious hypoglycemia (23) has been documented in which hypoglycemia was attributable to invitro utilization of glucose by the parasite. The metabolic and endocrine abnormalities are shown in Table 2.

DIAGNOSIS

Diagnosis of HAT involves a three-tiered approach for infections due to T.b. Gambiense and a two-tiered approach for that due to T.b. rhodosiense. The three steps for gambiense HAT include a screening test, diagnostic confirmation, and stage determination while that for rhodesiense HAT are diagnostic confirmation and stage determination. Screening is for gambiense HAT involves serology - CATT (Card Agglutination Test for Trypanosomiasis), which detects the presence of specific antibodies in the patient’s blood or serum. Diagnostic confirmation is done to detect the presence of trypanosomes in lymph node aspirates, chancre smear, or in blood. Stage determination is via the detection of trypanosomes (after centrifugation) and white cell count in the cerebrospinal fluid (lumbar puncture): Hemolymphatic stage is characterized by the absence of trypanosomes AND ≤ 5 white cells/mm³ and the Meningoencephalitic stage is defined by evidence of trypanosomes OR > 5 white cells/mm³.

Diagnosis of Chagas disease is via identification of Trypanosoma cruzi by direct microscopy of fresh blood or blood concentrated by the microhematocrit method. Serological tests for anti-Trypanosoma cruzi antibodies are performed for cases of suspected disease but no definitive diagnosis by microscopy.

PHARMACOTHERAPY FOR TRYPANOSMIASIS

Acute or chronic Chagas disease can be treated with either benznidazole or nifurtimox for those without cardiac or GIT complications. Drugs employed in the management of HAT include Nifurtimox, Eflornithine, Melarsoprol, Pentamidine, and Prednisolone (24).

CLINICAL PRESENTATION

Uncomplicated malaria presents with fever, headache, and generalized malaise. Severe malaria refers to the demonstration of asexual forms of the malaria parasites (commonly P falciparum) in a patient with a potentially fatal manifestations or complications of malaria. Severe malaria is characterized by altered mentation, severe hemolysis, some metabolic abnormalities, and organ complications.

ENDOCRINE AND METABOLIC ABNORMALITIES

Hypoglycemia is commonly documented in severe malaria and hyperglycemia although infrequently reported is seen in severe malaria as well as uncomplicated malaria. Hypocalcemia is also reported in severe malaria as well as in cases of uncomplicated malaria.

Hypoglycemia may be iatrogenic due to quinine administration or due to increased glucose turnover secondary to increased glucose uptake resulting from anaerobic glycolysis and alterations in glucose production in severe malaria (26). Nigeria Reports have hypoglycemia (blood glucose <2.2mmol/L) documented in 60% of children diagnosed with severe malaria (27). Hyperglycemia on the other hand infrequently occurs in persons with malaria and it may present in uncomplicated malaria or severe malaria due to P falciparum infection. The causes of hyperglycemia sometimes necessitate the temporary use of insulin and is multifactorial. These include release of counter-regulatory hormones in response to the stress of the underlying malaria disease condition and pro inflammatory cytokines which increase blood glucose (28). Other proposed reasons for hyperglycemia are reduced sensitivity to insulin and increased gastric and small intestine permeability for sucrose in malaria patients (29-30).

Hypocalcemia is reported in severe malaria as well as in cases of uncomplicated malaria. It has been shown that there is an inverse relationship between parasite load and calcium levels with calcium levels returning to normal following treatment and parasite clearance (31). Altered magnesium metabolism and disturbed parathyroid gland function have been documented as possible reasons for hypocalcemia in malaria (32).

The pituitary-thyroid axis may be depressed in severe malaria and this is most likely attributable to adaptations of the pituitary-thyroid axis to the underlying illness. A Report has noted suppressed T4 and TSH levels with a poorly responsive pituitary gland to TRH stimulation as evidenced by low TSH levels following stimulation (33-34). Another possible mechanism underlying the secondary hypothyroidism is parasitic sequestration within the hypothalamo-pituitary portal system (35).

Clinical and biochemical parameters of central diabetes insipidus which in some cases warranted treatment has been reported in severe malaria. The suggested mechanism is obstruction of the neurohypophyseal microvasculature (36-37).

Primary and secondary adrenal insufficiency which may present with subnormal cortisol levels and in some cases overt features of hypocortisolemia may be seen in severe malaria. Primary adrenal insufficiency may be due to necrosis or impaired circulation due to sequestration of parasites. Some reports have results suggestive of cytokines playing a role in modulating the hypothalamic-pituitary-adrenal axis in secondary adrenal insufficiency. Other potential mechanisms for secondary adrenal insufficiency are erythrocyte sequestration within the hypothalamic -pituitary portal system, altered setpoint for cortisol inhibition of ACTH, and production of a peptide like mammalian somatostatin which has been found to inhibit ACTH secretion in vitro (38-39).

DIAGNOSIS AND TREATMENT

Direct microscopy employed on thin and thick blood films enable parasite detection, species identification, quantification, and monitoring of parasitemia. Serology via the rapid diagnostic tests which detects the parasite antigen can be employed.

Figure 5:

Giemsa-stained peripheral blood smear. Arrow A showing a classic, ring-shaped trophozoite of Plasmodium falciparum. Arrow B showing a classic, headphone-shaped trophozoite of P. falciparum. Arrow C showing two trophozoites of P. falciparum within the same red blood cell. (Reproduced from BMJ Case Reports (Surce-Parikh et al. Classic image: peripheral blood smear in a case of Plasmodium falciparum cerebral malaria http://dx.doi.org/10.1136/bcr-2014-205820

Severe malaria regardless of the infecting specie is treated with intravenous Artesunate and interim oral treatment, artemether -lumefantrine. Other oral antimalarial drugs are Atovaquone-proguanil, Quinine. and Mefloquine.

TRANSMISSION

It is primarily an intestinal parasite in cats and has a wide host of intermediate hosts including sheep and mice and exists in three forms: oocysts, tachyzoites, and bradyzoites. Oocysts are only produced in the definitive host – the cat. When passed in the feces and then ingested, the oocysts can infect humans and other intermediate hosts where they develop into tachyzoites- rapidly multiplying trophozoite form of T. gondii. They divide rapidly in cells, causing tissue destruction and spreading the infection. The transmission of toxoplasmosis is shown in Figure 5. Tachyzoites in pregnant women are capable of infecting the fetus. Eventually tachyzoites localize to muscle tissues and the CNS where they convert to tissue cysts, or bradyzoites which is the dormant stage. This is thought to be a response to the host immune reaction. Ingestion of cysts in contaminated meat is also a source of infection, as bradyzoites transform back into tachyzoites upon entering a new host.

Figure 5.

Mode of transmission of toxoplasmosis

CLINICAL PRESENTATION

Toxoplasmosis is often asymptomatic or associated with mild self-limiting symptoms except in immunocompromised persons and sometimes in cases that are congenitally transmitted via the transplacental route (congenital toxoplasmosis).

CNS toxoplasmosis is one of the most common and important opportunistic infections in patients who are immunocompromised -the clinical manifestations are often nonspecific, with the most common presenting symptoms being headache, lethargy, fever, and focal neurologic signs. In congenital toxoplasmosis (CT), chorioretinitis is the most common manifestation and may cause seizure, hydrocephalus, and psychomotor delay.

ENDOCRINE AND METABOLIC ABNORMALITIES

Endocrine defects in toxoplasmosis are usually neuroendocrine in nature and may occur in congenital toxoplasmosis as well as acquired toxoplasmosis. Endocrine manifestations of Toxoplasmosis include hypogonadotropic hypogonadism, precocious puberty, short stature, and diabetes insipidus. Documented hormonal abnormalities in persons with congenital toxoplasmosis result from hypothalamo-pituitary dysfunction and include growth hormone, gonadotropin, and ADH deficiency (40-41) (Figure 6).

Figure 6.

Computerized tomography of brain showing dilated ventricles with multiple subependymal and parenchymal calcifications (arrow). (Source: Mohammed S et al; Congenital toxoplasmosis presenting as central diabetes insipidus in an infant: a case report BMC Res Notes. 2014; 7: 184.

Hypogonadotropic hypogonadism may occur transiently as a result of the modulation of the hypothalamus-pituitary axis by cytokines. Trypanosomiasis which is seen as a ring enhancing lesions in the brain during MRI imaging is an organic cause of the neuroendocrine abnormalities noted in some series (42-44).

Toxoplasmosis has been suggested as a possible risk factor for type 2 diabetes mellitus. Some Researchers have suggested that Toxoplasma gondii directly effects pancreatic cells through beta cell destruction (45-46).

DIAGNOSIS AND TREATMENT

Diagnosis is made via direct detection of the parasites in body fluid and tissue samples.

Serology and molecular techniques are also employed in the diagnosis. Imaging preferable MRI is of use in suspected CNS involvement. Pyrimethamine, Sulfadiazine and Trimethorprin, and sulfamethoxazole are pharmacotherapies for managing toxoplasmosis.