Comparison of blood and lymph node cells after intramuscular injection with HIV envelope immunogens.

Background: Harnessing CD4+ T cell help in the lymph nodes through rational antigen design could enhance formation of broadly neutralizing antibodies (bNAbs) during experimental HIV immunization. This process has remained hidden due to difficulty with direct study, with clinical studies instead focusing on responses in the blood as a proxy for the secondary lymphoid tissue. Methods: To address this, lymph node cells (LNC) were collected using ultrasound guided fine needle aspiration of axillary lymph nodes from 11 HIV negative participants in an experimental HIV immunogen study (European AIDS Vaccine Initiative EAVI2020_01 study, NCT04046978). Cells from lymph node and blood (PBMC), were collected after intramuscular injection with HIV Env Mosaic immunogens based on HIV Envelope glycoprotein and combined with a liposomal toll-like receptor-4 adjuvant; monophosphoryl lipid A. Simultaneously sampled cells from both blood and lymph node in the same donors were compared for phenotype, function, and antigen-specificity. Results: Unsupervised cluster analysis revealed tissue-specific differences in abundance, distribution, and functional response of LNC compared with PBMC. Monocytes were virtually absent from LNC, which were significantly enriched for CD4+ T cells compared with CD8+ T cells. T follicular helper cells with germinal center features were enriched in LNC, which contained specific CD4+ and CD8+ T cell subsets including CD4+ T cells that responded after a single injection with HIV Env Mosaic immunogens combined with adjuvant. Tissue-specific differences in response to an MHC-II dependent superantigen, staphylococcal enterotoxin B, indicated divergence in antigen presentation function between blood and lymph node. Conclusions: LNC are phenotypically and functionally distinct from PBMC, suggesting that whole blood is only a limited proxy of the T cell lymphatic response to immunization. HIV-specific CD4+ T cells in the lymph node are rapidly inducible upon experimental injection with HIV immunogens. Monitoring evolution of CD4+ T cell memory in LNC with repeated experimental HIV immunization could indicate the strategies most likely to be successful in inducing HIV-specific bNAbs.

Association of Dengue Virus and Leptospira Co-Infections with Malaria Severity.

Plasmodium infections are co-endemic with infections caused by other agents of acute febrile illnesses, such as dengue virus (DENV), chikungunya virus, Leptospira spp., and Orientia tsutsugamushi. However, co-infections may influence disease severity, treatment outcomes, and development of drug resistance. When we analyzed cases of acute febrile illness at the All India Institute of Medical Sciences, New Delhi, India, from July 2017 through September 2018, we found that most patients with malaria harbored co-infections (Plasmodium mixed species and other pathogens). DENV was the most common malaria co-infection (44% of total infections). DENV serotype 4 was associated with mild malaria, and Leptospira was associated with severe malaria. We also found the presence of P. knowlesi in our study population. Therefore, in areas with a large number of severe malaria cases, diagnostic screening for all 4 DENV serotypes, Leptospira, and all Plasmodium species should be performed.

Renal detection of Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi in malaria associated acute kidney injury: a retrospective case-control study.

OBJECTIVE: Acute kidney injury (AKI) is a frequent presentation in malaria infections. Several cases of AKI that are accompanied by clinical symptoms of malaria infection, such as fever, nausea, respiratory distress, and anemia remain undiagnosed due to challenges in accurate diagnosis using peripheral blood microscopy and rapid diagnostic tests that are currently used in clinical settings. This is particularly true for P. vivax and P. knowlesi infections. As a result, these patients are not able to receive anti-malarial therapy in a timely manner. The objective of the present study was to investigate if patients presenting with AKI harbored any of the five human Plasmodium species (P. falciparum, P. vivax, P. knowlesi, P. malariae, and P. ovale) within their renal tissues. RESULTS: We found that renal biopsies from malaria associated AKI patients harbor the human malaria parasites P. falciparum, P. vivax and P. knowlesi as mono- and mixed species infections. Presence of microvascular injury in a majority of the malaria associated AKI cases suggested vascular involvement of P. vivax and P. knowlesi. This research note also highlights P. knowlesi as an emerging pathogen in the Indian subcontinent.

An open trial of calcium dobesilate in patients with venous ulcers and stasis dermatitis.

BACKGROUND: Venous leg ulcers and associated stasis dermatitis are a major cause of morbidity, economic loss, and decreased quality of life in afflicted patients. Hence, there has been a renewal of interest in the medical management of varicose veins and ulcers. Calcium dobesilate, a capillotropic agent, has been found to be beneficial in the treatment of varicose veins. METHODS: This is an open pilot study of 25 patients (15 with venous ulcers with/without stasis dermatitis, 10 with stasis dermatitis only) who were given calcium dobesilate, 500 mg twice daily, for 8 weeks. The clinical parameters were graded (0-4; 0, absent; 1, mild; 2, moderate; 3, severe; 4, very severe) both before and after therapy, and included pain, itching, tiredness, heaviness, paresthesia, cramps, and leg swelling. Evaluation also included subjective changes in tenderness, oozing, and pigmentation, and measurement of the circumference of the leg for swelling and malleolar edema (measured in millimeters). The venous ulcer sizes were also recorded both before and after therapy. Color Doppler studies were performed to confirm the diagnosis of varicose veins, determine the competence of the valves, and to rule out deep vein thrombosis. Serum biochemistry, hemogram, and urinalysis were performed both before and after treatment. The results were analyzed statistically using the Wilcoxon rank sum test and Student's t-test. RESULTS: A statistically significant improvement was observed post-therapeutically in the clinical parameters of pain, itching, tiredness, heaviness, and leg swelling. There was also a significant decrease in ulcer size. The serum biochemistry, hemogram, and urinalysis remained unaffected. Color Doppler studies before treatment revealed venous valvular incompetence in 20 patients. They were repeated in only 10 patients after treatment, four of whom showed improved valvular competence. Recurrence of venous ulcers was seen in five of 12 patients who were followed up after therapy. No significant side-effects were noted. CONCLUSIONS: Calcium dobesilate is an effective adjuvant therapy, with an absence of significant side-effects, in patients with venous ulcers and stasis dermatitis. More double-blind trials are required in the future to substantiate and evaluate the role of the drug in these two indications.

Extensive fixed drug eruption to nimesulide with cross-sensitivity to sulfonamides in a child.

Nimesulide, a new nonsteroidal anti-inflammatory drug with a favorable tolerability profile, is being used increasingly in pediatric practice. Its common side effects pertain to the gastrointestinal tract and central nervous system. The common cutaneous adverse effects are pruritus and skin rash. Rarely purpura and fixed drug eruptions have also been observed in adults. We present herein a case of nimesulide-induced fixed drug eruption in a 10-year-old boy. The lesions were extensive and showed cross-sensitivity to sulfonamides.

The combination of glycolic acid peels with a topical regimen in the treatment of melasma in dark-skinned patients: a comparative study.

BACKGROUND: Melasma continues to be a difficult condition to treat, especially in dark-skinned patients, although various topical modalities including hydroquinone, tretinoin, and/or topical steroids have been used singly or in combination with variable results. OBJECTIVE: To determine if serial glycolic acid peels provide additional improvement when combined with a time-tested topical regimen, a modification of Kligman's formula (hydroquinone 5%, tretinoin 0.05%, hydrocortisone acetate 1% in a cream base). All cases had epidermal melasma as detected by Wood's light examination. METHODS: Forty Indian melasma patients were divided into two groups of 20 each. One group received serial glycolic acid peel combined with a topical regimen, modified Kligman's formula. The other, a control group, received only modified Kligman's formula. The results were evaluated by a clinical investigator both subjectively and with photographs taken at baseline, 12 (before the fourth peel), and 21 (3 weeks after the sixth peel) weeks. For clinical evaluation, the Melasma Area and Severity Index (MASI) was used. RESULTS: A significant decrease in the MASI score from baseline to 21 weeks was observed in both groups (P <.001). The group receiving the glycolic acid peels showed a trend toward more rapid and greater improvement, with statistically significant results (P <.001). Only a few side effects were observed in the peel group. CONCLUSION: This study demonstrates that serial glycolic acid peels provide an additional effect to a topical regimen which is a modification of the time-tested Kligman's regimen for treating melasma in dark-complexioned individuals if used judiciously and under supervision. It demonstrates that superficial chemical peels are beneficial in the treatment of melasma.

Cutis laxa in seven members of a north-Indian family.

Congenital cutis laxa, characterized by cutaneous laxity and loose skin, may be autosomal dominant or autosomal recessive. The autosomal dominant variety is usually not associated with any systemic defects and has a good prognosis. We report an unusual family in which seven members were affected by the autosomal dominant variant of this disorder. We suggest that close monitoring of the cardiorespiratory systems may be worthwhile to detect any systemic complications, although these complications are rare in the autosomal dominant variant of cutis laxa.

Squamous cell carcinoma in long-standing untreated lichen sclerosus et atrophicus of the penis.

Lichen sclerosus et atrophicus is an uncommon disease of skin and genital mucosa in both sexes. Involvement of the male genital mucosa is usually complicated by recurrent balanoposthitis, ulceration, phimosis, and meatal stenosis. The development of a squamous cell carcinoma is extremely rare in genital lichen sclerosus et atrophicus in males as compared with females. We report a 70-year-old male with a squamous cell carcinoma of the glans superimposed on long-standing lichen sclerosus et atrophicus of glans and prepuce. The patient in addition had a basal cell carcinoma on his face. Awareness of this rare complication of lichen sclerosus et atrophicus in males is emphasized.

Genital elephantiasis.

Genital elephantiasis (esthiomene), which is the dramatic end-result of lymphatic obstruction, is rather rare. Although mainly associated with filariasis and sexually transmitted diseases, such as lymphogranuloma venereum and donovanosis, it could also be an uncommon complication of tubercular lymphadenitis, a common infection in tropical countries. We report a rare case of a 32-year-old Indian female in whom genital elephantiasis occurred as a complication of tubercular lymphadenitis.

Human bite-induced penile ulceration: report of a case and review of literature.

Human bite on genitalia is a rare cause of penile ulceration, but is increasingly being reported, probably due to the increasing frequency of orogenital sex. The great morbidity associated with it brings it under the category of high-risk bite wounds, similar to those on hands, feet and joints. We report a case and review the literature on human bite-induced penile ulceration.