Clinical picture of cutaneous leishmaniases due to Leishmania (Leishmania) mexicana in the Yucatan peninsula, Mexico

Localized cutaneous leishmaniasis (LCL), known as "chiclero's ulcer" in southeast Mexico, was described by Seidelin in 1912. Since then, the sylvatic region of the Yucatan peninsula has been identified as an endemic focus of LCL. The purpose of the present work was to describe the clinical picture of LCL caused by Leishmania (Leishmania) mexicana in the Yucatan peninsula. A total of 136 cases of LCL, based on isolation and characterization of L. (L.) mexicana by isoenzymes and/or monoclonal antibodies, were selected. Some variability of clinical features regarding number, type, size, form, location and time of evolution of the lesions was observed. The most frequently observed presentation was a single, ulcerated, rounded small lesion, located on the ear, with an evolution time of less than three months, with neither cutaneous metastases nor lymphatic nor mucosal involvement. This picture corresponds to previous studies carried out in the same endemic area where an organism of the L. mexicana complex has been incriminated as a major aetiological agent of classical "chiclero's ulcer", confirming that in the Yucatan peninsula LCL due to L. (L.) mexicana when located on the pinna of the ear is a remarkable characteristic.

Leishmania (Leishmania) major-infected rhesus macaques (Macaca mulatta) develop varying levels of resistance against homologous re-infections

Seven rhesus macaques were infected intradermally with 10(7) promastigotes of Leishmania (Leishmania) major. All monkeys developed a localized, ulcerative, self-healing nodular skin lesion at the site of inoculation of the parasite. Non-specific chronic inflammation and/or tuberculoid-type granulomatous reaction were the main histopathological manifestations of the disease. Serum Leishmania-specific antibodies (IgG and IgG1) were detected by ELISA in all infected animals; immunoblot analyses indicated that numerous antigens were recognized. A very high degree of variability was observed in the parasite-specific cell-mediated immune responses [as detected by measuring delayed-type hypersensitivity (DTH) reaction, in vitro lymphocyte proliferation, and gamma interferon (IFN-gamma) production] for individuals over time post challenge. From all the recovered monkeys (which showed resolution of the lesions after 11 weeks of infection), 57.2% (4/7) and 28.6% (2/7) animals remained susceptible to secondary and tertiary infections, respectively, but the disease severity was altered (i.e. lesion size was smaller and healed faster than in the primary infection). The remaining monkeys exhibited complete resistance (i.e. no lesion) to each rechallenge. Despite the inability to consistently detect correlates of cell-mediated immunity to Leishmania or correlation between resistance to challenge and DTH, lymphocyte transformation or IFN-gamma production, partial or complete acquired resistance was conferred by experimental infection. This primate model should be useful for measuring vaccine effectiveness against the human disease.

Dissociation between vasodilation and Leishmania infection-enhancing effects of sand fly saliva and maxadilan

In this study, the ability of maxadilan and Lutzomyia longipalpis salivary gland lysate to enhance the infection of CBA mice by Leishmania major and of BALB/c mice by L. braziliensis was tested. No difference was observed between sizes of lesion in CBA mice infected with L. major and treated or not with salivary gland lysate or maxadilan, although they were injected in concentrations that induced cutaneous vasodilation. Although parasites were more frequently observed in foot pads and spleens of animals treated with maxadilan than in the animals treated with salivary gland lysate or saline, the differences were small and not statistically significant. The lesions in BALB/c mice infected with L. braziliensis and treated with maxadilan were slightly larger than in animals that received Leishmania alone. Such differences disappeared 14 weeks after infection, and were statistically significant only in one of two experiments.

Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania) major vaccines in a rhesus monkey (Macaca mulatta) model of the human disease

We have compared the efficacy of two Leishmania (Leishmania) major vaccines, one genetically attenuated (DHFR-TS deficient organisms), the other inactivated [autoclaved promastigotes (ALM) with bacillus Calmete-Guérin (BCG)], in protecting rhesus macaques (Macaca mulatta) against infection with virulent L. (L.) major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals), although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g) production or positive delayed-type hypersensitivity (DTH) response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05) between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

Efficacy of a diarylheptanoid derivative against Leishmania amazonensis

The activity of several diarylheptanoid derivatives (curcuminoids) was previously evaluated against Leishmania amazonensis promastigotes and among them the most active compound was the [1-(4-methoxy-phenyl)-7-(3,4-methoxy-4-hydroxy-phenyl)-1,6-heptadien-3, 5-dione]. This derivative was chosen to be assayed in vivo in a treatment trial. For these experiments, the curcuminoid compound was used in a concentration equivalent to the IC50/24 h, obtained from the previous study. Balb/c mice were inoculated subcutaneously in the footpad with L. amazonensis infective promastigotes and 4 weeks after the inoculation, the animals were treated with different schemes, varying from 1 to 3 doses. In all the experiments, Pentamidine Isethionate was used as reference drug under the same experimental conditions. The results showed that one dose was not enough to heal the lesion, however, with 2 and 3 doses the efficiency of the assayed compound was clear. On the other hand, treatment with Pentamidine Isethionate using the three different schemes was not satisfactory when compared to the curcuminoid derivative.

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061) were less frequent (= or < 2.5% each). The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.

Therapy of tungiasis: a double-blinded randomized controlled trial with oral ivermectin

Tungiasis is an ectoparasitosis causing considerable pathology in endemic areas. Standard therapy consists of removing the embedded parasite with a sterile needle. There is no effective chemotherapy at hand. To fill this gap, a double-blinded randomized controlled trial with oral ivermectin was conducted. A total of 54 individuals (27 in the placebo group, 27 in the ivermectin group) was followed up for seven days. They presented a total of 192 lesions. Patients received either ivermectin (300 µg/kg body weight at a single dose, repeated after 24 h) or placebo. Outcome measures included the clinical stage of lesion, presence of erythema, pain, itching, signs of viability of the parasite, and total lysis of flea. The ratio of fleas with total lysis per total number of fleas was slightly higher in the ivermectin group; however, this difference was not statistically significant. There was no significant difference in any of the other outcome measures between the treatment and the placebo group. The results show that oral ivermectin is without any clinically significant efficacy against embedded sand fleas at the dose given.

Malnutrition and hepatic fibrosis in murine schistosomiasis

In this paper, four different approaches attempting to reproduce the schistosomal liver fibrosis in undernourished mice are reported: shifting from a deficient to a balanced diet and vice-versa, repeated infections, influence of the genetic background, and immunological response. Infections were performed with 30 cercariae of Schistosoma mansoni and lasted at least four months. Undernourished mice were unable to reproduce the picture of "pipestem" fibrosis, except the C57 BL/10 inbred strain, four out of 21 mice developing the liver lesion. A link of this histological finding to the type of parasite strain can not be discarded at the moment. Repeated infections increased collagen deposition mainly in well nourished animals (seven out of 16 Swiss mice developed "pipestem"-like fibrosis). In undernourished infected Swiss mice the serum levels of soluble egg antigen specific antibodies IgG1, IgG2a, IgG2b, and IgG3 were two to four times lower than those detected for well nourished controls. The decreased humoral immune response coupled to the morphological, morphometric, and biochemical results reinforce the influence of the host nutritional status on the connective tissue changes of hepatic schistosomiasis.

Further observations on clinical, histopathological, and immunological features of borderline disseminated cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis

Leishmania (Leishmania) amazonensis has for some time been considered as the causative agent of two distinct forms of American cutaneous leishmaniasis (ACL): localized cutaneous leishmaniasis (LCL), and anergic diffuse cutaneous leishmaniasis (ADCL). Recently, a new intermediate form of disease, borderline disseminated cutaneous leishmaniasis (BDCL), was introduced into the clinical spectrum of ACL caused by this parasite, and in this paper we record the clinical, histopathological, and immunological features of eight more BDCL patients from Brazilian Amazonia, who acquired the disease in the Pará state, North Brazil. Seven of them had infections of one to two years' evolution and presented with primary skin lesions and the occurrence of metastases at periods varying from six to 12 months following appearance of the first lesion. Primary skin lesions ranged from 1-3 in number, and all had the aspect of an erythematous, infiltrated plaque, variously located on the head, arms or legs. There was lymphatic dissemination of infection, with lymph node enlargement in seven of the cases, and the delayed hypersensitivity skin-test (DTH) was negative in all eight patients prior to their treatment. After that, there was a conversion of DTH to positive in five cases re-examined. The major histopathological feature was a dermal mononuclear infiltration, with a predominance of heavily parasitized and vacuolated macrophages, together with lymphocytes and plasma cells. In one case, with similar histopathology, the patient had acquired his infection seven years previously and he presented with the largest number of disseminated cutaneous lesions. BDCL shows clinical and histopathological features which are different from those of both LCL and ADCL, and there is a good prognosis of cure which is generally not so in the case of frank ADCL.

Leishmania (Viannia) lainsoni: occurrence of intracellular promastigote forms in vivo and in vitro

Experimental chronic (45-day-old) skin lesion in hamster hind foot induced by Leishmania (Viannia) lainsoni infection showed the presence of promastigote forms in the tissue, inside parasitophorous vacuoles, as assessed by transmission electron microscopy. Experimental in vitro interaction (24 and 48 h) between Leishmania (V.)lainsoni and J774-G8 macrophage cells also demonstrated the same profile. This morphological aspect is unusual, since in this parasite genus only amastigote forms have been described as the resistant and obligate intracellular forms.

The girl from the Church of the Sacrament: a case of congenital syphilis in XVIII century Lisbon

Syphilis is a sexually or congenitally transmitted infectious disease with an impact on the health of human populations that has undergone important cycles in different countries and periods of history. Its presence was first diagnosed in Europe in the late XIV century. In Portugal, although there are various written records of the infection in the last centuries, there are rare references to it in archeological findings (mummified bodies are also rare in Portugal). The current study describes a probable case of congenital syphilis in an 18-month-old girl buried in the Church of the Sacrament in Lisbon. Her body, dating to the XVIII century, was found mummified together with dozens of others, still not studied. Symmetrical periostitis of the long bones, osteitis, metaphyseal lesions, left knee articular, and epiphyseal destruction, and a rarefied lesion with a radiological appearance compatible with Wimberger's sign all point to a diagnosis of congenital syphilis. The diagnosis of this severe form of the infection, possibly related to the cause of death in this upper-class girl, calls attention to the disease's presence in XVIII century Lisbon and is consistent with the intense mobilization at the time in relation to the risks posed by so-called heredosyphilis. It is the first case of congenital syphilis in a child reported in archeological findings in Portugal, and can be correlated with other cases in skeletons of adults buried in cemeteries in Lisbon (in the XVI to XVIII centuries) and Coimbra (XIX century). Finally, this finding highlights the need to study the entire series of mummified bodies in the Church of the Sacrament in order to compare the paleopathological findings and existing historical documents on syphilis, so as to expand the paleoepidemiological knowledge of this infection in XVIII century Lisbon.

Broken noses for the gods: ritual battles in the Atacama Desert during the Tiwanaku period

The sample consists of 226 skulls from the Atacameño cemetery of Coyo Oriente (639-910 AD), associated with the Tiwanaku period. The authors analyzed signs of acute trauma typically associated with violence, and the results were 12% of men and 9.9% of women displaying any type of lesion related to violence. In males, concentration of these non-lethal lesions in the nasal region (10.4%) as opposed to a random distribution over the entire skull (1.6%), suggests that the blows were struck during rituals. The cultural context of this period, with a strong ideological influence from Tiwanaku, supports the ritual hypothesis, since both the ethnographic as well as archeological records point to the existence of non-lethal violent bleeding with ritual beating to the face. Such rituals persist to this day among certain Andean populations. Among women, the most plausible hypothesis for the lesions (3.9% in the skull, 4.9% in the nasal bones, and 0.9% in the face) is domestic conflicts, since they show a random distribution. Previous studies with other Atacameño samples had indicated the same results for women.

Caries prevalence in skeletal series: is it possible to compare?

Because of the relationship with subsistence, dental caries is a central issue in paleopathological research. Usually, comparisons between caries prevalence exhibited in different skeletal series are made. Dietary variation is the most common explanation for cavities prevalence. The aim of this paper is to verify if it is possible to compare caries prevalence reported on papers for archaeological skeletal series. Another goal is to determine if other factors besides diet are implicated in dental cavity prevalence explanation. Twenty six papers about dental health with caries prevalences published from 1999 to 2004 were analyzed for completeness. This assessment includes carious lesion diagnosis and characteristics, age, sex and size characteristics of samples, and prevalence calculation method. The majority of the analyzed papers do not provide adequate information in the topics listed above. Only very few implicated factors other than diet as a contributor to caries lesions development.

Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl/6 mice

The critical role of interferon-gamma (IFN-g) in the resistance of C57Bl/6 mice to Leishmania major is widely established but its role in the relative resistance of these animals to L. amazonensis infection is still not clear. In this work we use C57Bl/6 mice congenitally deficient in the IFN-g gene (IFN-g KO) to address this issue. We found that IFN-g KO mice were as resistant as their wild-type (WT) counterparts at least during the first two months of infection. Afterwards, whereas WT mice maintained lesion growth under control, IFN-g KO mice developed devastating lesions. At day 97 of infection, their lesions were 9-fold larger than WT controls, concomitant with an increased parasite burden. At this stage, lesion-draining cells from IFN-g KO mice had impaired capacity to produce interleukin-12 (IL-12) and tumour necrosis factor-a in response to parasite antigens whereas IL-4 was slightly increased in comparison to infected WT mice. Together, these results show that IFN-g is not critical for the initial control of L. amazonensis infection in C57Bl/6 mice, but is essencial for the developmente of a protective Th1 type immune response in the later stages.

Prevalence of oral hairy leukoplakia and epithelial infection by Epstein-Barr virus in pregnant women and diabetes mellitus patients: cytopathologic and molecular study

Oral hairy leukoplakia (OHL) is generally reported in patients with severe immunosuppression, except for a few cases in individuals with moderate degree of immunodeficiency. It is a white lesion that appears mainly in the lateral border of the tongue, caused by Epstein-Barr virus (EBV). The nuclear changes caused by EBV (Cowdry A inclusion, ground glass and nuclear beading), observed in cytopathology, are specific and enough for the definitive diagnosis of OHL, independent of the identification of the virus. Here we investigated the prevalence of OHL and the presence of EBV-DNA in the lateral borders of the tongue from 90 pregnant women, 90 diabetes mellitus (DM) patients, 30 healthy individuals (negative group) and 30 HIV+ with OHL (positive group). Smears were analyzed by cytopathology and polymerase chain reaction (PCR). A case of subclinical OHL and candidiasis was identificated in a DM patient by cytopathologic analysis. PCR results demonstrated EBV-DNA in 65% of the pregnant women, in 35% of DM patients, and in 20% of the healthy individuals. We concluded that DM patients can develop OHL with a low prevalence. Furthermore, the prevalence of the EBV in lateral border of the tongue is larger in pregnant women than in healthy individuals.