Role of Bilastine in Allergic Rhinitis: A Narrative Review.

Allergic rhinitis (AR) is considered a trivial disease and is often self-treated with over-the-counter drugs and home remedies. However, AR is a contributing risk factor for asthma associated with complications, including chronic cough, eosinophilic esophagitis, and otitis media with effusion. In AR, inflammation is primarily mediated by histamines. Guidelines advise using second-generation oral H1 antihistamines as the primary treatment for AR. Second-generation H1 antihistamines strongly prefer the H1 receptor, limiting their ability to enter the central nervous system. Thus, they have minimal adverse effects. Among these H1 antihistamines, bilastine is highly specific for H1 receptors with a slight affinity for other receptors. It has a rapid and prolonged action, which reduces the need for frequent dosing and has better compliance. In the long term, bilastine is well-tolerated with minimal adverse effects. It is not associated with drug interactions, so dosage adjustment is unnecessary. Bilastine does not penetrate the brain and is nonsedating at 80 mg once daily. The low possibility of drug-drug interactions and pharmacokinetics of bilastine makes it suitable for elderly patients, even with compromised hepatic and renal function, without dose adjustment. This review comprehensively discusses the guidelines and the role of bilastine in treating AR. How to cite this article: Tiwaskar M, Vora A, Tewary K, et al. Role of Bilastine in Allergic Rhinitis: A Narrative Review. J Assoc Physicians India 2023;71(11):58-61.

SARS-CoV-2, Uncontrolled Diabetes and Corticosteroids-An Unholy Trinity in Invasive Fungal Infections of the Maxillofacial Region? A Retrospective, Multi-centric Analysis.

OBJECTIVES: Collate and analyse data of maxillofacial/rhino-cerebro-orbital fungal infections reported during the era of the Covid-19 pandemic, with the aim of investigating the common contributing factors leading to such infections and of highlighting the significance of this surge seen in patients infected with SARS-CoV-2. METHOD: This retrospective observational multi-centric study analysed patient data collected from clinicians belonging to different specialties in Bangalore, India. The data included the presentation and management of patients presenting with aggressive maxillofacial and rhino-cerebro-orbital fungal infections and explored the relationship between SARS-CoV-2, corticosteroid administration and uncontrolled diabetes mellitus. RESULTS: All 18 patients were Covid positive. Sixteen of the 18 patients received steroids for Covid treatment and 16 patients were diabetic (of whom 15 patients who were diabetics received steroids for Covid-19 treatment). Loss of vision was noted in 12 of the 18 patients and 7 of them underwent orbital exenteration. The fungi noted was mucormycosis in 16 patients, aspergillosis in 1 patient and a mixed fungal infection in 1 patient. Eleven of the patients survived, 6 died and 1 was lost to follow-up. There was a significantly higher incidence of diabetes (p = 0.03) amongst these cohort of patients who were Covid-19 positive with mucormycosis. A significantly higher number (p = 0.0013) of patients were administered steroids at some point during the treatment. CONCLUSION: Despite the limited sample size, it is evident that there is a significant increase in the incidence of angioinvasive maxillofacial fungal infections in diabetic patients treated for SARS-CoV-2 with a strong association with corticosteroid administration.

RAD6 promotes DNA repair and stem cell signaling in ovarian cancer and is a promising therapeutic target to prevent and treat acquired chemoresistance.

Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression. Upregulated RAD6 enhances DNA damage tolerance and repair efficiency of OC cells and promotes their survival. Increased RAD6 levels cause histone 2B ubiquitination-mediated epigenetic changes that stimulate transcription of stem cell genes, including ALDH1A1 and SOX2, leading to a cancer stem cell phenotype, which is implicated in disease recurrence and metastasis. Downregulation of RAD6 or its inhibition using a small molecule inhibitor attenuated DNA repair signaling and expression of cancer stem cells markers and sensitized chemoresistant OC cells to carboplatin. Together, these results suggest that RAD6 could be a therapeutic target to prevent and treat acquired chemoresistance and disease recurrence in OC and enhance the efficacy of standard chemotherapy.

Anti oxidant potential of Metformin and Pioglitazone in Type 2 Diabetes Mellitus: Beyond their anti glycemic effect.

OBJECTIVE: Insulin sensitizers might influence oxidative stress to improve insulin resistance in diabetes mellitus. The present study was designed with the aim to study the effect of Metformin & Pioglitazone on markers of oxidative stress after 4 weeks of therapy in patients with type 2 diabetes mellitus (Type 2 DM). RESEARCH DESIGN AND METHODS: This was a prospective study with follow up of 4 weeks in patients with Type 2 DM. They were randomized into metformin treated group (N=20) and Pioglitazone treated group (N=20) and healthy age-matched control group (N=20). Data was presented as mean±S.D. Student "t" test, ANOVA and Pearson correlation co-efficient tests were performed to analyze the parametric data in this study. RESULTS: Baseline clinical characteristics of the two study groups were similar. There is a significant difference for Fasting plasma glucose (FPG) and 2h-Post Prandial Plasma Glucose (PPPG) after 30 days of metformin and pioglitazone treatment. Metformin significantly reduced MDA (p=0.041) and increased SOD (p<0.001). Pioglitazone significantly reduced MDA (p<0.001) but failed to raise SOD level (p=0.132). Mean MDA was 4.57±0.57µM/L in metformin and 2.91±0.66µM/L in pioglitazone treatment with a p-value of <0.001. Further, a similar significant difference was obtained for SOD value by metformin and pioglitazone treatment (7.87±0.72U/ml vs. 6.94±0.53U/ml; p<0.001). CONCLUSION: Pioglitazone was superior to Metformin to improve oxidative stress as reflected by reduction in MDA but the antioxidant effect i.e. increase in SOD was seen with metformin only. The differing mechanism of actions of the two drugs on oxidative stress favors co prescription of these drugs for better outcome in improving insulin resistance and diabetic complications.

Objective criteria for diagnosing high altitude pulmonary edema in acclimatized patients at altitudes between 2700 m and 3500 m.

BACKGROUND: The criteria used for diagnosing high altitude illnesses are largely based on Western literature. This study was undertaken to define objective, simple and reliable diagnostic criteria for high altitude pulmonary edema (HAPE) in Indian soldiers at altitudes between 2700 m and 3500 m. METHODS: Clinical data of 235 cases of HAPE that occurred between 2700 m and 3500 m were analysed. Receiver operator characteristic (ROC) curve analysis was used to select simple clinical parameters suitable for the diagnosis of HAPE at peripheral medical facilities. Cut-off values and their reliability for the diagnosis of HAPE were defined. RESULTS: HAPE occurred 2.8 ± 2.2 days after arrival at altitudes between 2700 m and 3500 m. Breathlessness, cough, chest discomfort and headache were the commonest symptoms. Low pulse oximetry (SPO2) values than normal for this altitude were seen in 89% of patients. ROC analysis of clinical parameters identified a heart rate more than 95 beats per minute (bpm), respiratory rate more than 21 per minute and SPO2 less than 86% while breathing ambient air at this altitude as diagnostic of HAPE. The sensitivity and specificity of these cut-offs was 0.66, 0.83 and 0.82 and 0.94, 0.95 and 0.93 respectively. CONCLUSION: A heart rate of more than 95 bpm, respiratory rate more than 21 per minute and SPO2 less than 86% breathing room air in individuals complaining of breathlessness, cough, chest discomfort or headache within the first 5 days of arrival at altitudes between 2700 m and 3500 m is highly suggestive of HAPE.

Cutaneous T-cell lymphomas and their management strategies.

Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of lymphoproliferative disorders characterized by the proliferation of skin-homing post-thymic T-cells. It is the second most common extranodal non-Hodgekin's lymphoma. Many variants of mycosis fungoides and CTCLs are known to date, differing in clinical, histological, and immunophenotypic characteristics. Oral involvement has also been reported rarely in CTCLs. Treatment depends on the disease stage or the type of variant. New insights into the disease and the number of emerging novel therapeutic options have made it an interesting area for dermatologists and medical oncologists.

A study on evaluation of apoptosis and expression of bcl-2-related marker in wound healing of streptozotocin-induced diabetic rats.

Uncontrolled blood sugar is a major cause of vascular complications and delayed wound healing in diabetes mellitus. During wound healing process, normally, apoptosis is responsible for events such as removal of inflammatory cells and evolution of granulation tissue into scar which occur during the late phase of wound healing. Early apoptosis can lead to abnormal wound healing by removing granulation tissue including fibroblast, endothelial cell, and small vessels. To determine the role of apoptosis in association with hyperglycemia in diabetic wound healing, apoptosis-related intracellular marker such as expression of Bcl-2 protein by immunohistochemistry and normal histology has been studied. Histological findings show higher level of apoptosis and diminished granulation tissue formation in diabetic rats wounds along with minimal expression of Bcl-2 in diabetic rats wounds when compared with nondiabetic rats wounds. It can be concluded from this study that elevated blood sugar level may be associated with increased apoptosis and the least expression of Bcl-2 protein which might cause deregulation of the wound healing processes in streptozotocin-induced diabetic rats.

Study of Mutations in ß-Thalassemia Trait among Blood Donors in Eastern Uttar Pradesh.

BACKGROUND: Knowledge on distribution of different mutations of thalassaemia, which are prevalent in a particular area, is a prerequisite for prenatal diagnosis. OBJECTIVES: Studying mutations in ß - thalassaemia trait among blood donors in eastern Uttar Pradesh, India. MATERIAL AND METHODS: One thousand non - remunerated voluntary blood donors who were between 18 - 40 years of age, were included in the study. Both replacement and voluntary healthy blood donors were included. 4ml of venous blood was collected and it was stored at 4°C. Complete Blood Count (CBC), Haemoglobinopathy Screening and Molecular Analysis by ARMS - PCR (Amplification Refractory Mutation System - PCR) were done. Screening for ß thalassaemia was done in a blood bank by using D - 10, Bio Rad, which was based on High Performance Liquid Chromatography (HPLC). RESULTS: Twenty Eight subjects with ß- thalassaemia trait were found among 1000 voluntary blood donors. IVS 1-5 (G-C) mutation was most common type (50%), followed by FS 8/9 (+G) 25% which was the second most common type. In our study, a rare mutation of CD 16 (-C) was also found. Out of 14 subjects who had IVS 1-5 (G-C) mutation (most common), six were from Varanasi (6/261) and five of them were Sindhis. It was seen that FS 41/42 (TCTT) mutation was distributed among all groups of populations which had higher prevalences of ß-thalassaemia trait. CONCLUSION: A comprehensive knowledge on beta thalassaemia mutations is necessary for determining a prenatal diagnosis. The occurrence of mutations may vary according to geographic region. Therefore, this study dealt with current problem of unknown mutations, in order to avoid complications.

Pneumatocele in an adult.

We report a case of 25-year-old male who presented with high grade fever with cough and expectoration. Chest examination revealed amphoric breath sounds on the right interscapular region. Chest X ray revealed multiple air fluid levels with collapse lung at places. Staph pneumonia with pneumatoceles is common in children but uncommon to in adult population.

Very low frequency oscillations in the power spectra of heart rate variability during dry supine immersion and exposure to non-hypoxic hypobaria.

The origin of very low frequency (VLF) oscillations in the power spectra of heart rate variability (HRV) is controversial with possible mechanisms involving thermoregulation and/or renin-angiotensin-aldosterone system. Recently, a major contribution from vagal influences has been suggested. The present study investigated the behaviour of VLF (0.004-0.040 Hz) components of HRV power spectra in a group of healthy male volunteers during their exposure to (1) dry, supine, immersion in thermo-neutral water for 6 h (n = 7) and (2) non-hypoxic hypobaria (breathing 40-60% oxygen at 15,000' simulated in a decompression chamber) for 5 h (n = 15). The two manoeuvres are established to increase vagal outflow. During both the manoeuvres, all the frequency domain indices of HRV exhibited a significant increase. Increase in HRV was much more than that in the R-R interval. At 6 h of immersion, the R-R interval increased by ∼ 15% but the total power increased ∼ fourfold. Similarly, at 5 h of exposure to hypobaria, total power increased ∼ twofold with a very modest increase in an R-R of ∼ 9%. Increase in spectral power was appreciable even after normalization with mean R-R(2). Increase in VLF during immersion was more than reported during enalaprilat blockade of angiotensin convertase enzyme. Plasma renin activity did not vary during hypobaria. There was a significant increase in pNN50, an established marker of cardiac vagal activity. Centre frequencies of the spectra and slope (ß) of the relation between log(PSD) and log(frequency) did not change. Results were supportive of the notion that the parasympathetic system is pre-potent to influence slower (than respiratory) frequency components in HRV spectrum. Additionally, such an effect was without a change in the time constant of effector responses or pacemaker frequencies of VLF and LF periodicities and HRV was not a simple linear surrogate for cardiac vagal effects. An invariance of spectral exponent (ß) ruled out contamination of VLF and LF spectra from fractal power as an alternate explanation.

Pharmacognostical study of Tamalaki (Phyllanthus fraternus Webster), a herb used in Tamaka-svasa.

Tamalaki is a herbacious medicinal plant, described in Ayurvedic texts in many occurrences with different properties, actions, uses and synonyms, supposed to indicate more than one species commonly used in practice. Modern scholars mostly suggest Phyllanthus fraternus Webster (syn. P. niruri Linn.), P. amarus Schum. and Thonn. and P. urinaria Linn. as the source plants of Tamalaki. In this study, an attempt has been made to designate P. fraternus as the source plant of Tamalaki used in the treatment of Tamaka-svasa (Bronchial asthma) and other respiratory disorders by analyzing therapeutic uses, actions, properties, taste, synonyms as well as pharmacognostical characters. Smooth capsule, six tepals, less and short fibrous root, pentagonal outline with wing-shaped young stem are some of the specific characters observed in this species.

Targeting connexin 43 in diabetic wound healing: future perspectives.

The unknown mechanisms of impaired tissue repair in diabetes mellitus are making this disease a serious clinical problem for the physicians worldwide. The lacuna in the knowledge of the etiology of diabetic wounds necessitates more focused research in order to develop new targeting tools with higher efficacy for their effective management. Gap-junction proteins, connexins, have shown some promising results in the process of diabetic wound healing. Till now the role of connexins has been implicated in peripheral neuropathy, deafness, skin disorders, cataract, germ cell development and treatment of cancer. Recent findings have revealed that gap junctions play a key role in normal as well as diabetic wound healing. The purpose of this review is to provide the information related to etiology, epidemiology, clinical presentation of diabetic wounds and to analyze the role of connexin 43 (Cx43) in the diabetic wound healing process. The current control strategies and the future research challenges have also been discussed briefly in this review.

Effect of pioglitazone and rosiglitazone on mediators of endothelial dysfunction, markers of angiogenesis and inflammatory cytokines in type-2 diabetes.

The purpose of this study was to assess the effects of PPAR-gamma agonists (pioglitazone and rosiglitazone) on mediators of endothelial dysfunction and markers of angiogenesis in patients with type-2 diabetes. Pioglitazone group showed favorable reductions in serum total cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol and increase in HDL cholesterol as compared to rosiglitazone group, after 16 weeks of treatment and also with control group. There was significant reduction of CRP level in pioglitazone and rosiglitazone group. The level of serum TNF-alpha decreased significantly in pioglitazone and mildly decreased in rosiglitazone group. The level of VEGF, IL-8 and Angiogenin were increased in pioglitazone than rosiglitazone group. There were no significant changes observed in the serum angiogenin and IL-8 levels in the control group. Pioglitazone and rosiglitazone therapy in type-2 diabetes subjects have additional benefits of reducing mediators of endothelial dysfunction. Increase in angiogenesis markers in patients receiving pioglitazone could have variable effects in diabetic nephropathy and retinopathy as there may be increased vascular neogenesis. Pioglitazone has advantage over rosiglitazone in lowering lipid and proinflammatory cytokines.

Synthesis of carbon nanotubes using Ni95Ti5 nanocrystalline film as a catalyst.

Carbon nanotubes (CNTs) were synthesized by low-pressure chemical vapour deposition (LPCVD) using N2:C2H2:H2 gas mixtures on nanocrystalline Ni95Ti5 film. This nanocrystalline film was deposited on silicon substrate using vapour condensation method. The growth temperature and growth time was kept at 800 degrees C and 30 mins, respectively and the pressure was maintained at 10 Torr. The growth mechanism of CNTs was investigated using FESEM, TEM, HRTEM, and Raman Spectroscopy. From FESEM image of Ni95Ti5 nanocrystalline film, it is clear that the particle size varies from 5-10 nm. EDX analysis suggests that Ni95Ti5 alloy contains Ni and Ti both. It is clear from TEM images that CNTs are multiwalled with the diameter varying from 10-30 nm and length of several micrometers. HRTEM image shows that the structure of these multi-walled nanotube (MWNTs) is bamboo-shaped and the catalyst exists at the tip of MWNTs. Fourier Transform Raman Spectroscopy confirmed that graphitic structure of as-prepared CNTs. Field emission measurements reveal that the carbon nanotubes grown for 30 mins showed a turn-on field of 7.2 V/microm, when the current density achieves 10 microA/cm2. The field enhancement factor was calculated to be 708.50 for carbon nanotubes grown for 30 mins.

Decreasing incidence of renal cortical necrosis in patients with acute renal failure in developing countries: a single-centre experience of 22 years from Eastern India.

BACKGROUND: Renal cortical necrosis (RCN) accounts for 2% of all cases of acute renal failure (ARF) in adults and 15-20% of ARF during the third trimester of pregnancy in developed nations. However, RCN incidence is higher in developing countries ranging from 6-7% of all cases of acute renal failure. The present study describes changing trends in the clinical spectrum of RCN in patients with ARF in Eastern India. METHODS: Patients with ARF suspected to have RCN on clinical grounds underwent percutaneous renal biopsy. Patients showing cortical necrosis on histology were included in the present study. Diffuse and patchy cortical necrosis was classified based on standard histological criteria. The patients with cortical necrosis were studied over a period of 22 years; from July 1984 to December 2005. The results of our observation were compared with respect to etiology, incidence, prognosis and outcome of renal cortical necrosis in two study periods; namely, 1984-1994 and 1995-2005. RESULTS: The incidence of RCN was 3.12% of all cases of ARF of diverse etiology. RCN was observed in 57 patients; obstetric 32 (56.2%); non-obstetric 25 (43.8%). Diffuse cortical necrosis was the dominant lesion in 41 (71.9%) patients and the remaining 16 (28%) patients had patchy cortical necrosis. The overall incidence of RCN in obstetric ARF was 15.2%; the incidence being higher (11.9%) in the post-abortal group in comparison to 3.3% in late pregnancy. RCN had occurred complicating abruptio placentae, puerperal sepsis and postpartum haemorrhage (PPH) in late pregnancy, while septic abortion was the sole cause of RCN in early pregnancy. Haemolytic uraemic syndrome (HUS) was the major (31.5%) cause of RCN in the non-obstetric group and miscellaneous factors were responsible in seven (12.3%) patients. Partial recovery of renal function was observed in 11 (19.2%), and 16 (28%) patients had progressed to ESRD. The incidence of RCN decreased from 6.7% in 1984-1994 to 1.6% in 1995-2005 of total ARF cases. RCN following obstetrical complication decreased significantly; 4.7% in the 1990s to 0.5% of the total ARF cases, in the 2000s. The mortality decreased to 19% in 1995-2005 from the initial high mortality of 72% in 1984-1994. The renal prognosis improved as a result of the decreased mortality of patients. CONCLUSION: We observed a decreasing trend in the incidence of RCN in patients with ARF in recent years, which is associated with increased patient survival and better renal prognosis. This improvement was mainly due to declining incidence and severity of RCN in obstetrical ARF.

Acanthamoebae presenting as primary meningoencephalitis in AIDS.

A rare case of Acanthamoebae meningoencephalitis is diagnosed in cerebrospinal fluid (CSF) of a 24 years old male suffering from acquired immunodeficiency syndrome (AIDS) patient on the basis of bright field microscopy and culture growth on non-nutrient agar with Escherichia coli. This case illustrates that Acanthamoebae should be considered in the differential diagnosis of meningoencephalitis in AIDS in addition to tuberculosis and cryptococcus infection in tropical areas.

Primary amyloidosis presenting with predominant lymphnodal masses.

A 50 year young farmer presented with clinical features of bilateral carpal tunnel syndrome and generalized lymphadenopathy including paratracheal and retroperitoneal lymphodes. The histological diagnosis confirmed primary amyloidosis of lymphnodes. Presentation of primary amyloidosis as lymphnodal mass with deposition of amyloid in carpal tunnel is extremely rare and can only be diagnosed by histochemistry. The clinical response to drugs is variable and needs surgical intervention for decompressive therapy which can improve the symptoms of carpal tunnel syndrome.

Effect of glycaemic control on apoptosis in diabetic wounds.

OBJECTIVE: To study the effect of glycaemic control on apoptosis in chronic ulcers in diabetic patients and the differential roles of insulin and oral hypoglycaemic agents (OHAs). METHOD: Ten non-diabetic (group I) and 20 diabetic patients (groups II and III), with a wound of more than four weeks' duration, who were attending the wound clinic at University Hospital, Varanasi, India were recruited. The 10 patients in group 11 received insulin and the 10 in group III an oral hypoglycaemic agent; all had diabetic foot ulcers. Wound biopsy and other routine investigations were performed. Both DNA fragmentation and morphological changes under light microscopy (apoptotic index) were used as determinants of apoptosis. Different variables, including fasting and post-prandial blood sugar, serum low-density lipoprotein (LDL) and markers of microangiopathy, such as proteinuria and diabetic retinopathy, were compared with apoptosis. RESULTS: DNA fragmentation in groups I, II and III was 40.00 +/- 2.97, 45.26 +/- 3.21 and 60.8 +/- 3.13 respectively (p < 0.01). Near linear correlation was observed with blood sugar level, particularly post-prandial blood sugar (p < 0.05) and DNA fragmentation. DNA fragmentation was significantly correlated with serum LDL and proteinuria, and it was much greater in the OHA group than in the insulin group (p < 0.05). Similarly, in the diabetic patients with background retinopathy the DNA fragmentation was 46.50 +/- 3.42 (n=3) in the insulin group and 66.70 +/- 6.48 (n=4) in the OHA group (p < 0.05). CONCLUSION: There is a significant increase in apoptosis in diabetic wounds with poorly controlled blood sugar and microangiopathy. This increase was greater in patients on OHAs than those on insulin, and it contributes to delayed wound healing. Morphological markers do not appear to be a reliable index of apoptosis in the diabetic wound.

Mucocutaneous lesions in transplant recipient in a tropical country.

Dermatological manifestations are common in renal transplant patients, but differ markedly with ethnic group and geographical location. We studied mucocutaneous lesions in 54 renal allograft recipients (related donors = 30; unrelated donors = 24) living in tropical atmospheres. Their gender was 50 males, and 4 females ranging in age between 15 and 63 years (mean = 37.84 years). The mean duration of follow-up was 124 months (range = 4 to 173 months). All patients received kidneys from living donors and were kept on immunosupression with mean daily doses of prednisolone, azathioprine, and cyclosporine of 10.2 mg, 68.6 mg, and 252 mg, respectively. The mean trough concentration of cyclosporine was 185 ng/mL. The mucocutaneous lesions were divided into four groups: drug-induced (n = 24, 44.4%), fungal (n = 18, 33.3%), viral (n = 9, 16.6%), and bacterial (n = 10, 18.5%). Cushingoid features, gum hypertrophy, and hypertrichosis were seen in 7 (12.9%) patients. Steroid acne was seen in three cases. Pityriasis versicolor was the most common (20.3%) fungal infection of the skin. In addition, Tinea unguium and mucocutaneous candidiasis were noted in four and three cases respectively. Herpes virus infection (Herpes zoster 5; Herpes simplex 2) was noted in 7 (12.9%) cases. Chicken pox at 5 years posttransplant and cutaneous vasculitis associated with cytomegalovirus disease at 6 months posttransplant were seen in one case each. We have not seen warts in our patients. Pyogenic bacterial infection of skin in the form of abscess (n = 6), cellulitis (n = 3), and pyoderma (n = 1) were observed in 10 (18.5%) patients. Thus, drug-induced mucocutaneous side effects and skin fungal infections are the most common dermatological manifestations among renal transplant recipients living in a tropical country.