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The clinicopathological features of 25 children who died with protein-calorie malnutrition were studied. All but four subjects were found at necropsy to have nutritional thymectomy and all but 3 died of infectious diseases. The infectious agents were chiefly intracellular micro-organisms including miliary tuberculosis, Herpes simplex, varicella, measles, Pneumocystis carinii, and Plasmodium falciparum. Staphylococcal infections, salmonellosis, shigellosis, strongyloidiasis, and hookworm were other significant infectious agents. Nutritionally acquired defective immunity, especially cell-mediated immunity, probably permitted these infectious agents to multiply and to disseminate widely. [ABSTRACT FROM AUTHOR]

Two black African women and one black American man had carcinomas of cervix, perineum, and sigmoid colon, respectively. In each of these patients, trophozoites of Entamoeba histolytica had invaded the surface of the tumor, and in some areas had invaded more deeply into the stroma between the tumor cells. Although it is well known that cutaneous amebiasis of anus, penis, vulva, and cervix can mimic squamous cell carcinoma, it may be, perhaps, less well known that carcinomas at these sites may be colonized by trophozoites of E. histolytica. In patients with amebiasis but without an associated carcinoma, a correct diagnosis of amebiasis spares the patient unnecessary and sometimes mutilating surgery. But a diagnosis of amebiasis, when there is an unrecognized underlying carcinoma, delays effective treatment of the carcinoma. A smear that establishes a diagnosis of cutaneous amebiasis, therefore, should be followed by biopsy to exclude or confirm an underlying carcinoma.

Although Mycobacterium ulcerans elicits extensive necrosis of human skin and subcutaneous tissue, the specific cause of the necrosis has never been elucidated. In an attempt to define a toxic substance, 18 strains of M. ulcerans were inoculated into mice, and the progress of each infection was observed and compared with infections of other mycobacteria, including M. cheloni, M. marinum, and M. bovis. Culture filtrates and viable organisms of each of these mycobacteria were inoculated onto tissue culture cells. Inoculation of mouse footpads with M. ulcerans resulted in progressive infections, leading to ulceration and eventual death. Strains of M. cheloni, M. marinum, and M. bovis did not produce progressive infections in the mice. Culture filtrates of M. ulcerans produced severe cytopathogenic effects on tissue cells, but washed, viable organisms of the same strains had no cytopathogenic effect. Culture filtrates and viable organisms of M. cheloni, M. marinum, and M. bovis did not produce a cytopathogenic effect on the tissue cells. Viable organisms of selected strains of M. ulcerans and the culture filtrates of the same strains were inoculated into guinea pig skin. The culture filtrates and the viable organisms both caused focal necrosis and focal inflammation, changes that resemble those in the naturally occurring infection in man. Preliminary purification of the culture filtrate by ultrafiltration indicates that the toxic fraction has a molecular weight of approximately 100,000, and temperature studies indicate that the toxic fraction is heat labile.

An autopsy study of 60 patients with fungal infections of the heart was undertaken. The patients ranged in age from 2 months to 79 years. Fifteen of the patients had undergone cardiac surgery; neoplasms were found in 13, renal failure in eight, bacterial infections in five, liver disease in five, gastrointestinal disorders in five, and immune disease in four; two had been intravenous drug abusers; other miscellaneous disorders were observed in three. The fungal infection was limited to the myocardium in 27 patients and to the endocardium in 17 patients. Myocardium and endocardium were involved in nine patients and pericardium and myocardium in five; two patients had pericarditis alone. The most frequent organism was Candida (62 per cent). Aspergillus (12 per cent) and Phycomycetes (12 per cent) were also found frequently. In 51 patients (85 per cent) other deep organs, usually lung, kidney, brain, or spleen were involved. Cultures for fungus had been positive in 26 patients prior to death, and postmortem cultures were positive in 29 patients. Patients who had undergone cardiac surgery had a higher incidence of endocarditis (93 per cent), with Candida (53 per cent) being the most frequent cause. Patients who had received antineoplastic drugs, antibiotics, or corticosteroids had a higher incidence of myocarditis (79 per cent), again most often due to Candida (60 per cent).

The silvered leaf monkey (Presbytis cristatus) from South Kalimantan ( Borneo ), Indonesia is a natural host for a variety of filarial nematodes including Brugia malayi and Wuchereria kalimantani . Experimental studies show that it is host for W. bancrofti, a filarial nematode causing elephantiasis in man. Presbytis cristatus is a gregarious primate of primary and secondary forests, roaming in troops of 20-30 members. Primarily a fruit and leaf eater under natural conditions, this monkey can adapt to a laboratory diet of commercial monkey chow supplemented with fruits and vegetables. Troops, led by an alpha male, immediately respond to protect their young during stressful or dangerous situations. Infants are born singly and are bright orange. Transition to the adult grey and black coloration begins three to five months after birth. Silvered leaf monkeys can be readily trapped. Initially they are aggressive and will attack but become tractable several days after capture. Reaching upward is an important feeding behavior of the silvered leaf monkey and they will not feed from the floor of the cage. In the laboratory they are nonaggressive and lend themselves to various procedures such as blood drawing and examination. Silvered leaf monkeys travel well in commercial animal transport cages. In the United Stages they are not an endangered species and can be readily imported. In Indonesia they are not protected by law and can be exported.

One accidental and 17 natural human infections caused by Penicillium marneffei have been reported in the literature. The accidental infection, in Paris, followed inoculation of a culture from a Vietnamese bamboo rat into the finger of a mycologist. All patients with natural infections had lived or traveled in the Far East. Nine of these patients were Chinese, all from Guangxi Zhuang Autonomous Region. The four additional infections from Guangxi reported herein bring the total to 21 natural infections. P. marneffei is a primary pathogen of humans, causing two clinical types of disease: focal infection and fatal, progressive, disseminated infection. There are three histopathologic reactions: (1) granulomatous; (2) suppurative; and (3) anergic and necrotizing. The first two reactions are seen in patients with "normal" immunity and the third in patients with compromised immunity. P. marneffei is unique among species of Penicillium because of its thermal dimorphism, its recognized ecologic niche (restricted to the Far East), and its propensity to infect the lungs and the reticuloendothelial system and to proliferate within histiocytes.

We investigated the association between eosinophil degranulation, as evidenced by the deposition of granule major basic protein (MBP), and the killing of microfilariae of Onchocerca volvulus in vivo following treatment with diethylcarbamazine (DEC). Utilizing an immunofluorescence procedure for the cellular and extracellular localization of eosinophil MBP in formalin-fixed, paraffin-embedded tissues, we studied skin biopsies from onchocerciasis patients before and during treatment with topically or orally administered DEC. Before DEC, there was little or no inflammatory response in either dermis or epidermis and microfilariae were essentially intact. Immunofluorescent staining for MBP revealed some filamentous fluorescence associated with dermal collagen fibers, very few eosinophils, and no fluorescence in association with intact microfilariae. In contrast, during treatment with DEC, immunofluorescent staining for MBP revealed extensive eosinophil infiltrates in both dermis and epidermis with numerous intraepidermal eosinophil abscesses containing degenerating microfilariae. An intense extracellular immunofluorescence for MBP surrounded degenerating microfilariae in the dermis and epidermis in both the presence and absence of eosinophil infiltrates as early as 4.5 hours after starting therapy. Many intact nondegenerating microfilariae were also present, but they did not show immunofluorescent staining for MBP nor a surrounding inflammatory infiltrate. The results show that immediately following administration of DEC, eosinophils localize and degranulate around microfilariae in the skin and release granule MBP onto or in close proximity to the parasite's surface. Because of the striking association between eosinophil localization, degranulation, and deposition of MBP onto microfilarial surfaces, and the degeneration of microfilariae in the skin, these observations support the hypothesis that the eosinophil, through helminthotoxic granule proteins such as MBP, damages the microfilariae of O. volvulus.

Adult Mansonella perstans infected the abdominal cavity of nine patients seen at Karawa Hospital in the Ubangi territory of Zaire. In four patients the worms were removed at laparotomy, and in the other five they were removed at autopsy. Twelve adult worms were identified in the nine patients. None of the worms caused symptoms or contributed to the patient's death. Worms were in the hernial sac in three patients, and one each was in connective tissue beside a reactive mesenteric lymph node, in peripancreatic connective tissue, in perirenal connective tissue, in hepatic portal connective tissue, on the serosal surface of the small intestine, and in connective tissue adjacent to rectum. The diameter of male worms was 45 microns to 60 microns and of female worms, 80 microns to 125 microns. One female worm was removed intact. It was 6 cm long and had a bifurcated tail characteristic of M. perstans.

Onchocerciasis--infection by Onchocerca volvulus--has four cardinal manifestations: dermatitis, subcutaneous nodules, sclerosing lymphadenitis, and eye disease. The first three are discussed here. The dermatitis begins when microfilariae degenerate in the dermis. This process is accompanied by inflammation, with degranulation of eosinophils and deposition of the major basic protein of the eosinophil granules on the cuticle of the microfilariae. So far as is known, the chronic effects of onchocerciasis are all a consequence of the degeneration of microfilariae. Subcutaneous nodules contain coiled adult worms and have an outer layer of fibrous scar and a central inflammatory cell exudate, which may cavitate. Perfusion of India ink reveals arborization of capillaries around adult worms, which derive nutrition from these networks. Onchocercal lymphadenitis is characterized initially by histiocytic hyperplasia and follicular atrophy and later by fibrosis and obstruction of lymph flow, a condition causing adenolymphocele ("hanging groin") and elephantiasis of the genitalia. Some patients appear to have immune tolerance to degenerating microfilariae, perhaps as a result of exposure in utero to microfilarial antigens in the maternal circulation. In contrast, other patients (Yemenites, for example) have a localized but intense response to a few microfilariae; these patients are hypersensitive--perhaps because they were not exposed to microfilarial antigens in utero. Autopsy data on infection of deep organs are limited.

Two patients with Buruli ulcer (infection by Mycobacterium ulcerans) in the Foya region of Liberia have recently been reported. We describe three more patients which together with the two original patients establish the Mayor River basin as an endemic area of Buruli ulcer. We also describe a patient from the St. Paul River basin. This disease, unrecognized in Liberia before 1978, now seems to be widespread in Liberia and has been reported in neighboring Sierra Leone and observed in Ivory Coast as well. The possibility of Buruli ulcer appearing in other regions of West Africa should be anticipated. Diagnosis involves finding acid-fast bacilli in smears of the exudate from typical lesions or by finding in biopsy specimens the characteristic zone of coagulation necrosis containing acid-fast bacilli. The bacillus, Mycobacterium ulcerans, stains readily with the Ziehl-Neelsen (ZN) and Fite-Faraco (FF) procedures. Treatment is excision when the lesion is small and by debridement and grafting, combined with heat and chemotherapeutic agents when the lesion is large.

Clinicopathological studies on lymph nodes of 32 Africans with onchocerciasis--some complicated by hanging groin and elephantiasis of the genitalia--revealed atrophic lymphoid tissue, lymphoedema, chronic inflammation and fibrosis. We identified microfilariae of Onchocerca volvulus in nodes of 24 of 32 Africans (75%). There microfilariae were most numerous in the capsule and in the fibrous tissue of the medulla, but smaller numbers were also found within lymphoid tissue, in dilated lymphatics and in blood vessels. We believe that in Africians, antigens released from microfilariae of O. volvulus lead to the deposition of immune complex in tissues, which in turn causes inflammation and fibrosis and eventually obstructive lymphadenitis. This causes hanging groin and, possibly, also elephantiasis. A distinctive pattern of perivascular fibrosis contains "fibrinoid material" that we interpret as immune complexes involving microfilarial antigens. In contrast, nodes from two Yemenites with severe onchocercal dermatitis of the lower limbs (sowda) had hyperplastic follicles, minimal fibrosis and no microfilariae.

A case of pitted keratolysis caused by Dermatophilus congolensis is reported. The organism was isolated from the lesion and identified by its morphological, cultural, and biochemical characteristics. A survey of the literature revealed that it rarely causes human infections, but is a common causative agent of disease in domesticated and wild animals. Human infections reported previously were traced to contact with infected animals or contaminated soil. We report pitted keratolysis in a 44-year-old physician with no known history of such a contact.

Between July 1973 and December 1974, 304 autopsies were done at Hopital Mama Yemo, Kinshasa, Republic of Zaire. The causes of death and sudden death were tabulated and analyzed. The frequency of various diseases and groups of diseases among all the individuals and a large subset of individuals who died traumatically are tabulated and discussed. The present report is the most quantitative, albeit only, current estimate of mortality and prevalence of diseases in Zaire.

Specimens of skin from four Cameroon patients with severe onchocercal dermatitis, before and after treatment with diethylcarbamazine (DEC), were studied by light and electron microscopy. Microfilariae of Onchocerca volvulus have ultrastructural features resembling those of microfilariae of other genera. Between the surface layer of the cuticle and the trilaminate membrane, there is an electrolucent zone which is much wider in degenerating microfilariae than in intact microfilariae. Widening of the zone may result from DEC-induced release of component(s) of the cuticle, possibly collagen or mucopolysaccharide. Between the cuticle and dermal collagen there are granular deposits which might be immune complexes involving the collagenous component of cuticle. Others have shown that DEC does not kill microfilariae in vitro. Treatment with DEC presumably "unmasks" microfilariae in the skin so that they are recognized as foreign bodies and are destroyed by the host's defenses. Histiocytes and eosinophils are seen in close proximity to degenerating microfilariae. Enzymes from histiocytes and eosinophils might readily penetrate the cuticle altered by DEC treatment, and digest various components within the microfilariae. Alternatively, the widening of the electrolucent zone might result directly from the action of leucocytic or histiocytic enzymes, after the microfilaria has been killed by other mechanisms.

Three infants, born prematurely, died after clinical illnesses of 67, 65, and 60 days from infection by Malassezia furfur. Each infant had been nourished with lipid emulsions delivered through deep-line catheters. The infections, all discovered at autopsy, were characterized by massive involvement of lungs. Two of the three had endocardial vegetations containing M. furfur; all three had lesions in liver, kidney, and spleen, and two had lesions in adrenal, pancreas, and colon. In addition, one of the infants had acute meningoencephalitis caused by M. furfur. In some of the distant organs, yeast cells of M. furfur were growing in the lumina of small vessels, filling the lumina, but causing no vasculitis or infarction. In addition to these benign collections of yeasts within vessels, there were acute inflammatory lesions as well. These were consolidation, vasculitis, granulomatous inflammation, septic thrombosis, and septic infarction of lung and foci of necrosis and inflammation in kidney and liver. Two previously reported autopsies described neonates with lesions in lung and heart. The authors' three cases for which autopsies were performed had lesions in lung and heart too but, in addition, had dissemination with acute lesions in kidney and liver. Finally, one patient had a severe meningoencephalitis caused by M. furfur.

Liesegang rings (LRs) are periodic precipitation zones from supersaturated solutions in colloidal systems. They are formed by a process that involves an interplay of diffusion, nucleation, flocculation or precipitation, and supersaturation. Examples include LRs of calcium carbonate in oölitic limestone (in nature), LRs of silver chromate in gelatin (in vitro), and LRs of glycoprotein in pulmonary corpora amylacea (in vivo). Here we describe LRs in lesions from 29 patients--mostly lesions of the kidney, synovium, conjunctiva, and eyelid. The LRs formed in cysts, or in fibrotic, inflamed, or necrotic tissue. The LRs in this study varied greatly in shape and size, measuring 7-800 microns. Special stains and energy-dispersive radiographic analysis or scanning electron microscopy revealed that some LRs contained calcium, iron (hemosiderin), silicon, and sulfur. Some pathologists have mistaken LRs for eggs, larvae, or adults of the giant kidney worm, Dioctophyma renale. D. renale is a large blood-red nematode that infects a variety of fish-eating mammals, especially mink. Fourteen documented infections of humans have been recorded, usually with adult worms expelled from the urethra. The adult worms are probably the largest helminth to parasitize humans. Eggs of D. renale are constant in size (60-80 microns X 39-47 microns), contain an embryo, and have characteristic sculpturing of the shell. Liesegang rings should not be mistaken for eggs, larvae, or adults of D. renale, or for any other helminth.

Eight patients with fatal penicilliosis caused by Penicillium marneffei are reported. All were natives of southern rural Guangxi, and none had a predisposing illness or evidence of altered immunity. The distinctive features of P. marneffei include proliferation of yeast-like cells within histiocytes, followed by the development of focal necrosis and, eventually, large abscesses. Outside the histiocytes, the fungi elongate, become slightly curved, and form septa. In vitro, P. marneffei produces a red pigment which diffuses into the culture medium. The differentiation between P. marneffei and Histoplasma capsulatum is described, and possible reservoirs for P. marneffei are discussed.

The clinical and pathologic features of 25 cases of phaeomycotic cyst, collected at the Armed Forces Institute of Pathology between 1959 and 1978, are described. Phaeomycotic cyst is infection of the deep dermis and subcutaneous tissue by dematiaceous (brown) fungi. Species of Phialophora were most frequently isolated from these lesions. Synonyms for phaeomycotic cyst are--among others--phaeomycosis and phaeosporotrichosis. Phaeohyphomycosis includes phaeomycotic cyst and some other mycoses. The term "phaeo" is derived from the Greek phi alpha iota omicron sigma, meaning grey or black, and refers to the brown color in vivo and in vitro of these fungi. Phialophora species are world-wide saprophytes, common in soil, decaying wood, and vegetation. They have low virulence and low pathogenicity, and are inoculated along with slivers whose retention is probably an important causal factor in establishing infection. Proliferation of the fungi provokes a mixed suppurative and granulomatous reaction which remains localized. Early the characteristic histopathologic picture is one of multiple stellate abscesses. These progress to a single circumscribed lesion with a central cavity filled with pus and surrounded by a fibrous wall. There are no systemic signs or symptoms, regional lymph nodes are not involved, nor has any patient had systemic spread. The infection is rare but tends to be more common in warm climates. No race, sex, or age group is predisposed, but patients with immune deficiency or debilitating disease are at increased risk. In older publications phaeomycotic cysts have been described as variants of chromomycosis, sporotrichosis, and mycetoma. Phaeomycotic cysts, however, do not provoke hyperplasia of the epidermis or ulceration--characteristic features of both chromomycosis and sporotrichosis, nor do phaeomycotic cysts form sinus tracts or contain grains--both typical features of mycetoma. The strictly localized abscess or "cyst" is the characteristic feature of phaeomycotic cysts.