Malaria and Less Common Protozoan and Helminth Infections

Parasitic infections are highly prevalent in many developing areas of the world and are common among pregnant women in developed countries. They may exacerbate maternal and fetal anemia, and contribute to low birth weight and poor infant survival. The placenta serves as an effective barrier, even in infections such as malaria and schistosomiasis in which systemic involvement and hematogenous spread are common. Although transplacental infections of the fetus are uncommon, the prevalence of parasitic infections among infants younger than 1 month is high in developing countries, and infections occur primarily through transmission during or shortly after birth.

In a study conducted in Guatemala, Kotcher and colleagues found that 30% of newborns had acquired a protozoal infection by 2 weeks of age. Although these infants were infected with Entamoeba histolytica , Entamoeba coli, Endolimax nana, and Iodamoeba buetschlii, they remained asymptomatic. Giardia lamblia was found by the fifth week of life and Trichuris trichiura by the 16th week of life. A study conducted in a regional hospital in Togo revealed that 55% of infants and children from birth to 16 years of age demonstrated evidence of parasitic infections in stool or urine, with obvious neonatal infections occurring as well.

Soil-transmitted helminths (STHs), primarily Ascaris, Trichuris, and hookworm, through gastrointestinal infection and chronic blood loss, can result in or exacerbate iron deficiency anemia and nutritional deficits. Worldwide, it is estimated that more than 1 billion people are infected with at least one STH, including at least 44 million pregnant women infected with hookworm alone. Although few random controlled trials have failed to demonstrate a beneficial impact of anthelmintics in pregnancy, results from observational studies suggest a potential benefit on maternal anemia, birth weight, and infant mortality, and further studies are needed.

Pneumocystis jirovecii (previously classified as Pneumocystis carinii ) is considered in Chapter 34 .

Ascaris

Ascaris lumbricoides is the most prevalent parasitic infection worldwide, affecting up to 1 billion people. In humans, Ascaris eggs are ingested through fecal-oral contamination, hatch in the small intestine, and then penetrate the intestinal lumen to migrate extensively through blood and lymphatics. Larvae eventually reach the pulmonary circulation, where they migrate into the alveolar sacs, through the respiratory tree to the esophagus, and into the small intestine. Because Ascaris may migrate to many organs, worms are occasionally found in the uterus and the fallopian tubes.

Human fetuses apparently can mount an immune response to maternal Ascaris infection, and congenital infections are rare. Sanjeevi and associates studied the immunoglobulin G (IgG) and IgM responses to Ascaris antigens from matched maternal and cord bloods in south India and found evidence of fetal IgM directed against Ascaris antigens in 12 of 28 samples. Clinical status of the infants was not reported. Chu and coworkers, however, described an infant whose delivery was complicated by the simultaneous delivery of 12 adult A. lumbricoides worms. During preparations for a cesarean section, which was being undertaken because of prolonged premature labor and fetal distress, one worm passed from the vagina, and another was found in the vagina. When the placenta was removed, 10 worms were found on the maternal side of the placenta. The infant was delivered in good condition. The infant passed two female worms, which were 28 and 30 cm long, on the second and sixth days of life. He was treated with piperazine citrate, but no other worms were passed, and no eggs were seen after the 11th day of life. Fertilized ova of A. lumbricoides were found in the amniotic fluid and in the newborn’s feces. An adhesion connected the mother’s intestine and uterus, but it is uncertain whether the worms passed directly from the mother’s intestine to the placenta and amniotic fluid, and were swallowed by the fetus; whether larvae passed hematogeneously from the mother’s lung to the placenta and thereby reached the fetal circulation, lung, and gastrointestinal tract; or whether female worms in the placenta produced fertile eggs that reached the amniotic fluid and were swallowed by the fetus. Other investigators have reported fetal evidence of Ascaris infection in infants as young as 1 to 2 weeks of age and in one infant with failure to thrive and bloody diarrhea at 3 weeks who responded to levamisole therapy.

Giardiasis

Giardia lamblia causes a localized intestinal infection, with no systemic involvement, and G. lamblia infection in pregnancy has not been associated with fetal infection. Severe maternal infection that compromises nutrition can affect fetal growth, but such a severe illness is rare. Neonatal G. lamblia infection can result from fecal contamination at birth. Infected infants are usually asymptomatic. Treatment of pregnant women with giardiasis is generally deferred until after the first trimester unless symptoms are severe. There is some evidence that maternal antibody may be protective against neonatal giardiasis.

American Trypanosomiasis: Chagas Disease

Millions of people in Central and South America are infected by Trypanosoma cruzi and related protozoa. Because of the chronicity of these infections, they have a significant impact on public health. One estimate suggests that approximately 40,000 women and 2000 newborns may be infected on an annual basis in North America, primarily in Mexico, although up to 3780 infected pregnant women and 189 congenitally infected infants could be born among Hispanic populations in the United States.

The Organism

The form of the organism that circulates in human blood is the trypomastigote. Cell division does not occur in the bloodstream. In tissue, the flagellum and undulating membrane are lost, and the organism differentiates into a leishmanial form, the amastigote. Amastigotes multiply by binary fission, and masses of amastigotes are grouped into pseudocysts. The amastigotes in pseudocysts may evolve into trypanomastigotes and, on rupture of the pseudocyst, can gain access to the bloodstream or to new cells. Two strains of T. cruzi that cause human infections have been identified by biochemical differences among nine enzymes produced by the parasite.

Epidemiology and Transmission

T. cruzi infects primates, marsupials, armadillos, bats, and many rodents, including guinea pigs, opossums, and raccoons; birds are not infected. Infection of insects and mammals with T. cruzi is most common between the latitudes 398N (i.e., northern California and Maryland) and 438S (i.e., southern Argentina and Chile) and on the islands of Aruba and Trinidad. The usual vectors are in the family Reduviidae, subfamily Triatominae. The main vector in Venezuela is Rhodnius prolixus ; in Brazil, Panstrongylus megistus ; and in Argentina, Triatoma infestans (cone-nosed bug). These species are well adapted to human dwellings. Triatominae are hematophagous insects. They acquire and transmit the infection by biting infected vertebrates, including humans. The life span of the insect is not shortened by infection with T. cruzi ; infected insects live up to a year after the onset of infection. In North America, the sylvatic habitat of the vector and the low virulence of the strains of Trypanosoma are responsible for the relative rarity of the disease. Colloquial terms used for the usual vector include the kissing or assassin bug in the southwestern United States; pito, hito, or vinchuca in Spanish America; and barbeiro in Portuguese America.

The vector is most commonly found in huts of mud and sticks and in other housing containing cracks. In vectors infected with T. cruzi, metacyclic trypomastigotes congregate in the rectum. Bites become contaminated when defecation occurs. The infective form reaches the bloodstream through the site of the bite or by penetrating mucous membranes, conjunctivae, or abraded skin. Trypanosoma rangeli is spread by a few species of the triatomid bug. These metacyclic trypanosomes develop, divide, and multiply in the salivary gland. They are injected directly into the site of the bite.

Infections can also be acquired by blood transfusion and transplacentally. The isoenzyme patterns of T. cruzi recovered from congenitally infected infants and their mothers are identical, but transplacental transmission may not always follow maternal infection with enzymatically similar strains.

Pathology

Placenta

The placenta is a relatively effective barrier to the spread of infection to the fetus. The organism reaches the placenta by the hematogenous route and traverses the placental villi to the trophoblasts. After differentiation into amastigotes, the organism remains within Hofbauer (phagocytic) cells of the placenta until it is liberated into the fetal circulation.

Maternal parasitemia is greatest in the acute phase of infection; however, the period of intense parasitemia is short. Of the reported cases of congenital Chagas disease, only four have originated during the acute phase of infection. Most congenital infections occur in infants born to women with the chronic form of the disease.

Infected placentas are pale, yellow, and bulky. They have an appearance similar to the placentas of infants with erythroblastosis fetalis. Infection of the placenta is much more common than infection of the fetus.

Biopsy and Autopsy Studies

Two histologic types of lesions are recognized: those that contain parasites and those that do not. In tissue sections, the parasite assumes the morphology of Leishmania bodies, which are round and contain an ovoid nucleus and a rodlike blepharoplast. Inflammation usually does not occur unless a pseudocyst ruptures. Tissue reactions induced by an antibody are believed to be responsible for lesions in which the parasite cannot be demonstrated. After infection, an antibody that cross reacts with the endocardium, the interstitium, and the blood vessels of the heart is formed and is referred to as an endocardial-vascular-interstitial antibody. This antibody has an affinity for the plasma membranes of the endocardium, endothelial cell, and striated muscle, and for T. cruzi . Endocardial-vascular-interstitial antibody is present in 95% of persons with Chagas heart disease and in 45% of asymptomatic patients with serologic evidence of having had Chagas disease.

Tissue replication of the organism causes damage to the ganglia of the autonomic nervous system and to muscle. Injury to the Auerbach plexus results in megaesophagus, megacolon, and dilatation of other parts of the gastrointestinal tract and gallbladder. Similarly, the conducting system of the heart and the myocardium may be infected. Sudden death from arrhythmias can occur.

Clinical Manifestations

In the mother, urticaria is often present at the site of the bite, regardless of whether the insect was infected. The favored site for the bite is the face, presumably because this is the part of the body that is most often exposed during sleep. In acute infections, an inflammatory nodule, referred to as a chagoma, may develop at the site of the bite. If the bite is on the face, it is often associated with a unilateral, nonpurulent edema of the palpebral folds and an ipsilateral regional lymphadenopathy (i.e., Romaña sign). Between 2 and 3 weeks after the bite, parasitemia, fever, and a moderate local and general lymphadenopathy develop. The infection can extend and involve the myocardium, resulting in tachycardia, arrhythmia, hypotension, distant heart sounds, cardiomegaly, and congestive heart failure. The latter feature is more severe in pregnant and postpartum women than in nonpregnant women. Hepatosplenomegaly and encephalitis also occur. The mortality rate during the acute phase is 10% to 20%. Death is usually attributed to cardiac dysfunction. Many survivors have abnormal electrocardiograms.

In the chronic phase, the placenta and fetus may be infected despite the fact that the mother is asymptomatic. Chronic Chagas disease often comes to medical attention because of the occurrence of an arrhythmia. These patients often do not have signs or symptoms of congestive heart failure. Of 503 patients with myocardiopathy of chronic Chagas disease studied by Vasquez, 19.8% died during an observation period of 6 years—37.5% suddenly and 55.2% with congestive heart failure.

Abortions and Stillbirths

Of 300 abortions in Argentina, 3 (1%) were performed because of Chagas disease. In Chile and Brazil, 10% of all abortions are attributed to Chagas disease. When the fetus is aborted, massive infection of the placenta is usually found.

Congenital Infections

Bittencourt and coworkers found T. cruzi antibodies in 226 of 2651 pregnant women; 28.3% of seropositive mothers had parasitemia. Nevertheless, the risk of transmission to the fetus is low, and live births of infants congenitally infected with T. cruzi are rare. It is postulated that upregulation of fetal or neonatal immunity might be important in preventing vertical infection. Congenital infections occur in 1% to 5% of women with serologic evidence of having had Chagas disease. ^∗

∗ References .

Among infants with a birth weight of 2500 g or more, congenital infections are rare. Among low-birth-weight infants, congenitally infected infants can be premature or small for gestational age, or both. Congenital infections were found in 10 (2.3%) of 425 infants by Saleme and associates in Argentina, in 10 (2%) of 500 infants weighing less than 2000 g by Bittencourt and coworkers in Brazil, and in 3 (1.6%) of 186 infants with birth weights of more than 2000 g and in 1 (0.5%) of 200 premature infants with birth weights of 2000 g or less by Howard in Chile.

Congenitally infected infants may develop symptoms at birth or during the first few weeks of life. Early-onset jaundice, anemia, and petechiae are common. These symptoms are similar to those associated with erythroblastosis fetalis. As occurs in older patients, congenitally infected infants may have hepatosplenomegaly, cardiomegaly, and congestive heart failure and have involvement of the esophagus leading to dysphagia, regurgitation, and megaesophagus. Some infants have myxedematous edema. Pneumonitis has been associated with infection of the amnionic epithelium. Congenitally infected infants can be born with encephalitis or can develop it postnatally. It is generally associated with hypotonia, a poor suck, and seizures. The cerebrospinal fluid shows mild pleocytosis, which consists primarily of lymphocytes. Cataracts and opacification of the media of the eye have also been observed. Both twins may be congenitally infected, or one may escape infection.

Of 64 congenitally infected infants for whom follow-up results were known, Bittencourt reported that 7.8% died the first day, 35.9% died when younger than 4 months, 9.3% died between the ages of 4 and 24 months, and 42.2% survived for more than 24 months. Of those who survived for 2 years or longer, 74% had no serious clinical symptoms despite continued parasitemia. However, subclinical abnormalities might have been found if electrocardiography or radiography had been performed.

As with other congenital infections, the immune system of the fetus is stimulated. IgM antibody to T. cruzi and endocardial-vascular-interstitial antibody are formed.

Diagnosis

The diagnosis should be suspected at the time of abortions and stillbirths, and in infants who develop symptoms compatible with congenital infection. An easy, but often omitted, means of making a diagnosis of congenital infection is to examine the placenta for the amastigote of T. cruzi . The gross appearance of the placenta is similar to that seen in erythroblastosis fetalis. It appears that examination of infected amniotic fluid by polymerase chain reaction is not useful in diagnosing congenital infection.

Motile trypomastigotes can also be demonstrated by examining blood under a coverslip. The number of parasites is low initially but increases subsequently. Thin and thick smears can be examined after being stained with Giemsa stain. Microhematocrit concentration and examination of the buffy coat enhance the detection of parasites in congenital Chagas disease. If more than 10 parasites/mm ³ are found, the infant generally dies.

Xenodiagnosis is performed by allowing laboratory-bred uninfected insects to feed and ingest the patient’s blood. The fecal contents of the insects are examined for trypomastigotes 30 to 60 days later. Blood may also be injected into mice. In mothers with acute Chagas disease, the parasites are found in blood smears beginning 3 weeks after onset of the infection, and they persist for several months. Parasites can be demonstrated for years by xenodiagnosis.

In the chronic stages of the disease, the diagnosis can be made histologically by sampling skeletal muscle. The histologic appearance of the parasite in tissue sections is similar to that of toxoplasmosis. However, the amastigotes in Chagas disease contain a blepharoplast that is lacking in toxoplasmosis.

Several tests for antibody are available. Complement-fixing antibody crosses the placenta from mother to infant. This test, referred to as the Machado-Guerreiro reaction, demonstrates antibodies that exhibit a cross-reaction with Leishmania donovani and with sera from patients with lepromatous leprosy. In uninfected infants, complement-fixing antibodies are no longer demonstrable after the 40th day of life; in infected infants, these antibodies persist.

Agglutinating antibodies may also be demonstrable. Uninfected infants with titers of agglutinating antibody of 1:512 or less at birth have negative titers by 2 months of age. The titer of agglutinating antibody in uninfected infants with initial titers of 1:1024 or higher becomes negative by 6 months of age. IgM fluorescent antibodies can be demonstrated in some infants, but infected infants do not always have a positive test result. Data suggest that fetal IgG to specific acute-phase antigens may be useful in the diagnosis of congenital Chagas disease, but maternal and neonatal serologic tests using the microhematocrit, direct parasitologic visualization, and indirect hemagglutination or enzyme-linked immunosorbent assay have proved to be reliable.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here