Anti-Wolbachia therapy for onchocerciasis & lymphatic filariasis: Current perspectives

Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.

Hepatitis B & C virus infection in HIV seropositive individuals & their association with risk factors: A hospital-based study

Background & objectives: Hepatitis B and hepatitis C virus (HBV and HCV) cause acute and chronic hepatitis, and infections with HBV and HCV are common in HIV-infected patients. The present study was conducted to determine the co-infection of hepatitis B and C virus in stored serum samples of HIV-positive/negative individuals attending an Integrated Counselling and Testing Centre (ICTC) in north India and their association with certain risk factors. Methods: This study included a total of 840 serum samples, of which 440 were from HIV seropositive individuals and 400 were from control individuals seeking voluntary check-up of HIV status at ICTC. Serum samples were used for the detection of HBV and HCV infection. Results: HBV infection (11%) was found to be less in contrast to HCV (13%) amongst the HIV seropositive. In controls, HBV and HCV infection was two and three per cent, respectively. Co-infection of HBV and HCV was found in 15 of 109, and in controls, it was 2 of 15. Age group between 21 and 40 was significantly associated with HBV and HCV infection. Heterosexual contact was the leading mode of acquiring HBV and HCV infection. Interpretation & conclusions: HBV and HCV co-infection was found to be significantly higher in HIV-positive individuals in comparison to normal population. Hepatitis virus infection leads to rapid progression of liver cirrhosis in HIV-infected patients. Routine check-up of HIV seropositive patients for hepatitis virus may be required to monitor clinical outcome.

Vaccination Policy for Japanese Encephalitis in India: Tread with Caution!.

Live attenuated SA-14-14-2 vaccine against Japanese encephalitis (JE) was introduced in the routine immunization under Universal Immunization Program in the 181 endemic districts of India. Recently, the Government of India has announced the introduction of one dose of JE vaccine for adults in endemic districts. The policy to mass vaccinate adults has raised several concerns that are discussed in this write-up. Apart from adult vaccination, the continuation of large scale JE vaccination program despite it being a very focal problem, and continued neglect of some other serious public health illnesses have also been highlighted. The issue of lack of authentic data on effectiveness of currently employed SA-14-14-2 JE vaccine has also been discussed.

Vaccines for fungal infections

High morbidity and mortality caused by mycotic infections has been a cause for concern. Trials for various vaccines against fungal pathogens have not been approved by the US Food and Drugs Administration because of the high cost of production and lack of a single suitable candidate. Most fungal infections require cell-mediated immunity for their clearance. This has been the basis for the development of various vaccines. We discuss the various trials of candidate vaccines, the protective efficacy as well as their shortcomings. Recent research suggests that a universal vaccine can be prepared which may be effective against most fungal pathogens.

Cryptosporidium in Children with Diarrhea: A Hospital-based Study.

Objective: To estimate the proportionate contribution of Cryptosporidium to diarrhea in under-five children, and to study its demographic and clinical associates Methods: We collected stool specimens from children (age <5 yrs) suffering from diarrhea. The specimen was examined on the same day by Kinyoun’s acid-fast staining for the presence of Cryptosporidium parvum oocyst; rest of the sample was preserved for later cryptosporidium antigen detection by commercially available ELISA kit. Results: Out of 175 children with diarrhea, 48 (27.4%) had Cryptosporidium antigen in their stool specimen. Gender, history of contact with domestic animal, hydration status, breastfeeding and nutritional status were not significantly associated with cryptosporidium infection in children with diarrhea. Conclusion: Cryptosporidium is present in a significant portion of children suffering from diarrhea in our setting. Antigen detection has much higher isolation rate than acid-fast staining.

Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Mynmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

Immune response to second dose of MMR vaccine in Indian children.

Background & objectives: MMR vaccine in a two dose schedule has successfully eliminated measles, mumps and rubella from many developed countries. In India, it is not a part of national immunization programme but is included in the State immunization programme of Delhi as a single dose between 15-18 months. This prospective study was carried out to assess the extent of seroprotection against these three diseases in immunized children and to study the immune response to a second dose of MMR. Methods: Consecutive children aged 4-6 yr, attending the immunization clinic of a tertiary care hospital in Delhi for routine DT vaccination, were enrolled. Second dose of MMR was given and pre- and post-vaccination antibody levels were compared. Results: The pre-vaccination percentage seropositivity observed in the 103 children recruited, was 20.4 per cent for measles, 87.4 per cent for mumps and 75.7 per cent for rubella. Amongst the 84 children who were followed up after the second dose, the percentage seroprotection for measles rose from 21.4 (18/84) to 72.6 per cent (61/84) and 100 per cent became seroprotected to mumps and rubella. Interpretation & conclusions: The percentage of children protected against measles was found to be alarmingly low which needs to be investigated. Though the observed protection against mumps and rubella was adequate, its durability was not known. The need for re-appraisal of the current MMR immunization policy is called for by carrying out longitudinal studies on a larger sample.

Serological profile of HSV-2 in patients attending STI clinic: Evaluation of diagnostic utility of HSV-2 IgM detection.

Objective: The present study was done to evaluate the serological profile of herpes simplex virus-2 (HSV-2) among patients attending sexually transmitted infections (STI) clinic and to determine the utility of detecting HSV-2 IgM antibodies in such patients. A correlation of HSV-2 infection with other STI including HIV has also been attempted. Materials and Methods: Hundred consecutive patients who attended STI clinic, with one or more of the complaints as enunciated by WHO in syndromic approach for the diagnosis of STI, were included as subjects. All subjects were screened for common STI by standard laboratory procedures/ commercially available kits. HSV-1 and HSV-2 IgM antibody was detected by commercially available enzyme immuno assay kit in all patient's sera. Sera were also tested for other STI, namely HIV, Hepatitis B virus, Hepatitis C virus and Treponema pallidum. Antigen detection for Chlamydia trachomatis was done in genital swabs of all patients by Bio-Rad Chlamydia Microplate EIA 31189 (United States) kit. Results: Thirty patients were found to have genital herpes. In 17/30 (56.6%) patients, HSV-2 serology was found to correlate with the clinical diagnosis. The coexistence of other infection in HSV-2 seropositive patients was detected in 8/30 patients. None of the patients having concomitant infections were clinically diagnosed accurately. Sensitivity, specificity, positive predictive value and negative predictive value of IgM antibodies for the diagnosis of genital herpes was 73.91%, 90.91%, 70.83% and 92.91% respectively. Conclusion: HSV-2 IgM detection could only be used as a supportive test for the diagnosis of genital herpes . It needs to be emphasized that the sensitivity and positive predictive value scores are pointers for further improvement in the commercial assay systems and a large sample size may determine the broader utility of such systems.

Antimicrobial susceptibility profile of Neisseria gonorrhoeae at STI clinic.

A total of 100 consecutive patients who attended a sexually transmitted infections clinic were studied. Thirteen had gonococcal urethritis, of which 10 showed growth of Neisseria gonorrhoeae on culture. All the isolates were tested for antimicrobial susceptibility by Australian Gonococcal Surveillance Programme (AGSP) method and beta lactamase production by chromogenic cephalosporin test. Four patients were co-infected with each of the following: HIV, HBV and Chlamydia trachomatis . Gonococcal urethritis (13%) was found more in male patients. Ten percent gonococcal isolates were penicillinase-producing N. gonorrhoeae , and another 10% were tetracycline-resistant N. gonorrhoeae .

Cytomegalovirus and rubella infection in children and pregnant mothers--a hospital based study.

Cytomegaloviruses (CMV) are ubiquitous and species-specific. Humans are believed to be the only reservoir of this virus and transmission occurs by direct or indirect person-to-person contact. Vertical transmission can lead to serious congenital infections. Rubella virus causes serious disease after vertical transmission but mostly remain subclinical or cause a trivial infection that may remain unrecognized. The objective of our study was to find the prevalence of CMV and rubella infection in the vulnerable section of our population attending GTB hospital. GroupI included pregnant women with bad obstetric history (BOH) (n=1115); GroupII normal pregnant women (n=500); Group III pediatric age group (n==585) and Group IV others with varied illness (n=100). Serologically IgM antibodies against CMV and rubella were detected using commercially available Elisa kit. The percentage prevalence in groupI was (11%) and (3.6%); groupII was (4%) and (0); groupIII was (12%) and (3%); group IV was (5%) and (1%) against CMV and rubella respectively. No apparent seasonal variation was observed in the pattern of infection. Also, overall infection rates were at a much lower rate as compared to other studies. Therefore the detection of IgM antibodies in early pregnancy is an important tool to identify active infection and to provide obstetric management to avoid the risk of congenital transmission of infection. This in turn may lead to a rethinking of current immunization strategies and appropriate modifications for the prevention of vertical infection.

Edible vaccines: current status and future.

Edible vaccines hold great promise as a cost-effective, easy-to-administer, easy-to-store, fail-safe and socioculturally readily acceptable vaccine delivery system, especially for the poor developing countries. It involves introduction of selected desired genes into plants and then inducing these altered plants to manufacture the encoded proteins. Introduced as a concept about a decade ago, it has become a reality today. A variety of delivery systems have been developed. Initially thought to be useful only for preventing infectious diseases, it has also found application in prevention of autoimmune diseases, birth control, cancer therapy, etc. Edible vaccines are currently being developed for a number of human and animal diseases. There is growing acceptance of transgenic crops in both industrial and developing countries. Resistance to genetically modified foods may affect the future of edible vaccines. They have passed the major hurdles in the path of an emerging vaccine technology. Various technical obstacles, regulatory and non-scientific challenges, though all seem surmountable, need to be overcome. This review attempts to discuss the current status and future of this new preventive modality.

Cytomegalovirus infection in neonates following exchange transfusion.

OBJECTIVES: This study was undertaken to ascertain the acquisition of cytomegalovirus infection following exchange transfusion and factors affecting such transmission in newborn infants at a tertiary care hospital in India. METHODS: Neonates undergoing double volume exchange transfusion (for any indication) with whole blood in the Neonatal Intensive Care Unit were enrolled over a 8 month period. Serum samples from the infant were collected for CMV serology before exchange transfusion, and at 6 and 12 weeks following the exchange. CMV serology was also conducted on samples obtained from the respective maternal and donor blood. RESULTS: Of 47 neonates who received exchange transfusion during the study period; only 26 (55.3%) neonates were finally followed up till 12 weeks of age. Only 3 (11.5%) children demonstrated CMV seroconversion during follow-up; all were low birth weight and small for gestational age. None of them demonstrated any clinical, hematological, biochemical, or radiological signs suggestive of perinatal CMV infection either at birth or during the course of follow-up. CONCLUSION: Exchange transfusion in neonates can result in perinatal transmission of CMV infection in low birth weight neonates. Such transmission does not result in any immediate manifestations. Data are not sufficient to warrant routine CMV screening of donor blood for exchange transfusion in our setting.

Interaction of potassium phosphonate fungicide in laterite soil.

Potassium phosphonate is a fungicide widely used to control Phytophthora fungi species in many crops all over the world. In this paper, an attempt has been made to study the interaction of potassium phosphonate with soil under varying pH and calcium level. Several reports available in literature indicate that the phosphonate in organic form adsorb strongly on almost all mineral surfaces and natural materials like soil and sediments. The present study conducted on laterite soil of Kerala using 2 mm sieved sample indicated that phosphonate obeys Freundlich adsorption isotherm. Though at lower concentrations, Langmuir model equally fits well, deviation was observed at higher concentrations. pH and calcium content of the soil had striking influence on the interaction of the chemical with the soil. The calcium source also appeared to influence the adsorption phenomenon. Since potassium phosphonate is extensively used to control Phytophthora fungi species in black pepper (Piper nigrum) plantations in India and liming is a standard practice followed as soil amendment in acid soils to increase the soil pH, this study may help to maintain good soil quality.

Primary esophageal T-cell non-Hodgkin's lymphoma.

Primary non-Hodgkin's lymphoma of the esophagus is a rare disease. We report a 52-year-old man who had a polypoid mass in the esophagus at endoscopy. Histology was suggestive of non-Hodgkin's lymphoma; immunohistochemistry was positive for CD3, CD45 RO, LCA. He was treated with 6 cycles of CHOP and is disease-free 14 months later.

Risk taking behavior and Sexually Transmitted Diseases: a study among men.

Sexually Transmitted Diseases (STDs) among men not only jeopardize their own health but also increase sexual morbidities among their spouses. STDs are primarily attributed to high-risk sexual behavior. The study was carried out among male patients attending the OPD of a Government dispensary. Risk taking behavior was assessed using a structured, pre-tested questionnaire and STDs were diagnosed using syndromic approach supported by laboratory investigations. Three hundred two men were selected by systemic random sampling for inclusion in the study. 39% had pre-marital sexual relationship, 20% had sex with Commercial Sex Workers. 12% of the married men had extramarital sex mostly with CSWs. 27% had more than one sex partner ever. Only 3.6% used condoms consistently. Thirteen per cent respondents had history of symptoms suggestive of STDs. Prevalence of syphilis, gonorrhea and other STDs among study subjects were 3.6%, 0.7% and 0.7% respectively. High risk sexual behavior is widely prevalent and STDs are also common. Behavior change communication and early diagnosis and prompt treatment of STDs will reduce the burden significantly.

Immunogenicity of low dose intradermal hepatitis B vaccine and its comparison with standard dose intramuscular vaccination.

OBJECTIVE: A prospective study was carried out in the well baby and immunization clinics of tertiary care hospital to compare the immunogenicity of low dose hepatitis B vaccine (HBV) given intradermally versus standard dose given intramuscularly. METHODS: One hundred ninety six term, healthy, Australia antigen negative and exclusively breast fed babies were allocated into two groups in a simple randomized manner. In group I, hepatitis B vaccine was given in low dose (2 mcg) by intradermal route whereas in group II it was administered in standard dose (10 mcg) by intramuscular route. Diphtheria, pertussis, tetanus (DPT) and oral polio vaccine (OPV) were co-administered with HBV in both the groups at 6, 10 and 14 weeks of age at different sites. One hundred seventy seven infants could be regularly followed up and tested for anti-HBs titres by third generation ELISA test using mono-ELISA anti-HBs 3.0 kits. Geometric mean titres of anti-HBs were estimated in each group and compared. Student's t-test was used for statistical analysis.RESULTS: Seroprotective anti-HBs titres (titre greater than 10 mIU/mL) were achieved in 87 of 88 (98.8 percent) children having received intramuscular doses as compared to 82 of 89 (92.1 percent) children in the intradermal group. The geometric mean titres of the intradermal group were 92.71 mIU/mL (95 percent C.I. 68.85-124.85), significantly lower than 331.66 mIU/mL (95 percent C.I. 245.12-448.78), noticed in the intramuscular group. There were no significant adverse reactions in both the groups. Hepatitis B vaccine is immunogenic when co-administered with DPT and OPV vaccine. The intradermal hepatitis B administration is less effective with lower immunogenicity than the intramuscular vaccination.

Prenatal diagnosis of Glanzmann thrombasthenia.

BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet function, which results in major morbidity due to persistent, spontaneous, mucocutaneous bleeding and menorrhagia in women. Platelet transfusions are often needed to control the bleeding. Glanzmann thrombasthenia results from mutations in the genes located on chromosome 17q21-23, encoding the platelet glycoprotein (GP) IIb/IIIa receptor. METHODS: This report describes, for the first time in India, the prenatal diagnosis performed in a family who had a child with GT. As the molecular defect had not been identified at the time of chorionic villus sampling (CVS), prenatal diagnosis was done by linkage assessment. Haplotype analysis was performed using polymorphic markers on chromosome 17q 12-21, which included the dinucleotide repeat polymorphisms (CA)n in BRCA1 gene and locus D17S579 and (CT)n within GP IIIa intron 6, and the known restriction fragment length polymorphism (RFLP) markers Fok I (GP IIb exon 26), Taq I (GP IIIa exon 8) and Sma I (GP IIIa exon 9). The specific mutation in this family was subsequently confirmed. RESULTS: Both parents and the foetus were heterozygous for all the dinucleotide repeat polymorphisms and the affected child was homozygous. Both parents and the affected child were homozygous for Fok I RFLP. The father was heterozygous, and the mother, affected child and foetus were homozygous for Taq I and Sma I. The Fok I RFLP was identical for all the family members and hence did not provide any information for haplotype analysis (foetus not tested). CONCLUSION: The findings from dinucleotide repeat polymorphisms in BRCA1, D17S579, and GP IIIa intron 6 and the Sma I and Taq I RFLPs in GP IIIa strongly suggested that the foetus had inherited the father's mutant and the mother's normal alleles. Hence, the foetus was diagnosed to be a heterozygous carrier of GT by haplotype analysis. A private sequence alteration was later identified in the affected child in GP IIIa IVS1 (-14C --> A). The parents and foetus were heterozygous for this mutation. This confirmed the findings of the haploytpe analysis.