A comparative clinical study to assess safety and reactogenicity of a DTwP-HepB+Hib vaccine.

Hepatitis B and Haemophilus influenzae type b (Hib) infections are major public health problems in developing countries, including India. Hence, combination vaccines containing DTwP, recombinant hepatitis B and Hib conjugate vaccines have been developed. Here, we report a Phase IV study which assessed safety and reactogenicity of a new DTwP-HepB+Hib vaccine. Three doses of DTwP-HepB+Hib vaccine (Pentavac, Serum Institute of India Ltd) or Tritanrix-HB+Hib (GlaxoSmithKline Beecham) were administered to infants at 6, 10 and 14 weeks of age in 2:1 ratio. The subjects were followed till one month after the third dose for safety assessment. Adverse events were captured in structured diaries and physical examinations were performed on each visit. The study was conducted in 1510 infants. Both vaccines caused injection site local and systemic reactions and the incidence was similar in both the groups. The incidence of local solicited reactions was: tenderness 35.9 %-33.6 %; redness 18.1 %-17.2 %; swelling 23.7 %-22.4 %; induration 12.8 % -13.7 %. The percentage of systemic solicited reactions were: diarrhea 2.2 %-2.2 %; drowsiness 3.3 %-3.4 %; fever 14.0 %-11.2 %; irritability 28.1 %-25.4 %; loss of appetite 6.6 %-5.6 %; persistent crying 17.7 %-15.7 %; vomiting 3.5 %-3.0 %. No serious adverse event was caused by the vaccines. The new DTwP-HepB+Hib combination vaccine showed similar safety profile to that of an imported vaccine in Indian infants.

Persistence of antibodies induced by measles-mumps-rubella vaccine in children in India.

Antibody levels in 41 Indian girls were measured 6 years after measles-mumps-rubella (MMR) vaccination. Rates of seropositivity were 88% (measles antibodies), 95% (mumps antibodies), and 100% (rubella antibodies). The MMR vaccine induces long-term immunity in a majority of vaccinees; however, due to the observation of some seronegative vaccinees, the policy of administering a second dose of the MMR vaccine seems appropriate.

Immunogenicity of a new, low-cost recombinant hepatitis B vaccine derived from Hansenula polymorpha in adults.

BACKGROUND: Hepatitis B virus (HBV) infection is highly prevalent world over, especially in developing countries. A new recombinant hepatitis B virus (GeneVac-B; Serum Institute of India Ltd.) vaccine is developed using Hansenula polymorpha yeast. We decided to assess the immunogenicity, and reactogenicity of this vaccine in a large adult population. MATERIAL AND METHODS: Seven hundred eighty-eight adults subjects (age: 19-57 years, male:female ratio 35:1) received three 20 microg doses of a H. polymorpha-derived recombinant hepatitis B vaccine in months 0, 1, and 6. All the eligible subjects had negative baseline serum HBs Ag, and anti-HBs. The anti-HBs titer was obtained 1 month after the last dose of vaccine and was considered seroconverted if more than 1 mIU/ml, and seroprotective if more than 10 mIU/ml. RESULTS: The seroprotection rate was 96% and seroconversion rate was 97%. Seroconversion and seroprotection rates declined with increasing age. The minimum geometric mean titre of anti HBs was 443 mIU/ml (95% CI 407-482). Seroprotection was 96% in age group<40 years, while the same was 91% in >40 years group (Odd's ratio-2.9100, Z value-2.6183, highly significant). No other factor like smoking, tobacco-chewing, alcohol consumption, chronic diseases, and obesity, affected the immune response. No significant adverse reactions were reported in any of the subjects. CONCLUSIONS: Three standard doses of the H. polymorpha-derived recombinant HBV vaccine are highly immunogenic and safe in a predominantly male adult population. Young adults respond better with this vaccine. Because of its low cost, the vaccine may be a good choice in prevention of hepatitis B infection.

Feasibility of voluntary counselling and testing services for HIV among pregnant women presenting in labour in Pune, India.

Factors affecting the eligibility and acceptability of voluntary counselling and rapid HIV testing (VCT) were examined among pregnant women presenting in labour in Pune, India. Of the 6702 total women appearing at the delivery room from April 2001 to March 2002, 4638 (69%) were admitted for normal delivery. The remaining women presented with obstetrical complications, delivered immediately or were detected to be in false labour. Overall, 2818 (61%) of the admitted women had been previously tested for HIV during their pregnancy. If previously seen in the hospital's affiliated antenatal clinic, the likelihood of being previously tested was 89%, in contrast to 27% of women having prenatal care elsewhere. Of the admitted women, 3436 (74.3%) were assessed for their eligibility for rapid HIV VCT in the delivery room. Only 1322 (38%) of these women were found to be in early labour and without severe pain or complications, and therefore eligible for rapid HIV screening in the delivery room (DR). Of those 1322 eligible women, only 582 (44%) consented and were tested for HIV, of whom nine (1.6%) were found to be HIV-infected. Of the 1674 women arriving in the DR with no evidence of previous HIV testing, through this DR screening programme, we identified four women with HIV who could now benefit from treatment with ART. Given the high rates of HIV testing in the antenatal clinic at this site and the challenges inherent to conducting DR screening, alternatives such as post-partum testing should be considered to help reduce maternal to infant transmission in this population.

No definitive evidence for L-Zagreb mumps strain associated aseptic meningitis: a review with special reference to the da Cunha study.

The study by da Cunha et al. published in 2002 reported that MMR vaccine containing L-Zagreb mumps strain manufactured by Serum Institute of India Ltd. caused a high incidence of aseptic meningitis (AM) from routine surveillance during two mass immunization campaigns (MIC) conducted in 1998 in two states in Brazil. Since the results were contrary to those in India, Egypt and Bahamas, a critical analysis of the study was done. Several inconsistencies were found in the study, which undermined the conclusions drawn. Two similar studies from Brazil reported similar results. Review of these studies and those done on the vaccine from Zagreb, Croatia showed that in no study the L-Zagreb mumps virus has been isolated from cerebrospinal fluid (CSF) of an AM case. Isolation of the vaccine virus is necessary for definite causal association of AM with the vaccine. There is no such evidence to causally link MMR vaccine containing L-Zagreb mumps strain with AM.

Profile of bone marrow examination in HIV/AIDS patients to detect opportunistic infections, especially tuberculosis.

Morphological evaluation of 140 bone marrow aspirations received in haematopathology laboratory with serologically established HIV infection, along with other relevant special haematological tests, was done during 1st Jan 1999 - 31st Dec 2002 at state government run tertiary care General Hospital in Maharashtra state, India. Out of 140 cases: 118 (84.28%) patients had anaemia, 25 (17.86%) had leukopenia, while 13 (9.28%) were thrombocytopenic. Dyserythropoiesis was present in 18 (12.86%) cases, dysmyelopoiesis 37 (26.43%) and micromegakaryocytes were noted in 44 (31.43%) cases. Haemophagocytosis was evident in 8 (5.71%) cases. Plasmacytosis encountered in 120 (85.71%) cases was a common feature. Based on clinical profile and results of other investigations 56 (40%) patients were clinically diagnosed to be of Mycobacterium tuberculosis (TB). Of these, 18 (12.86%) bone marrow aspirates were positive for AFB, Mycobacterium tuberculosis. In 4 cases cryptococci were demonstrated (Mucicarmine stain). There was one case each of Histoplasma capsulatum and leishmaniasis. One patient showed dense parasitemia with Plasmodium falciparum. One patient had immunoblastic lymphoma and showed bone marrow infiltration. Findings in this study strongly indicate that in HIV/AIDS, AFB stain should be done on each marrow aspirate to rule out tuberculosis in countries like India; where TB and AIDS are marching together.

Optimizing the HIV/AIDS informed consent process in India.

BACKGROUND: While the basic ethical issues regarding consent may be universal to all countries, the consent procedures required by international review boards which include detailed scientific and legal information, may not be optimal when administered within certain populations. The time and the technicalities of the process itself intimidate individuals in societies where literacy and awareness about medical and legal rights is low. METHODS: In this study, we examined pregnant women's understanding of group education and counseling (GEC) about HIV/AIDS provided within an antenatal clinic in Maharashtra, India. We then enhanced the GEC process with the use of culturally appropriate visual aids and assessed the subsequent changes in women's understanding of informed consent issues. RESULTS: We found the use of visual aids during group counseling sessions increased women's overall understanding of key issues regarding informed consent from 38% to 72%. Moreover, if these same visuals were reinforced during individual counseling, improvements in women's overall comprehension rose to 96%. CONCLUSIONS: This study demonstrates that complex constructs such as informed consent can be conveyed in populations with little education and within busy government hospital settings, and that the standard model may not be sufficient to ensure true informed consent.

Awareness of HIV/AIDS and household environment of pregnant women in Pune, India.

Our objective was to determine the level of HIV/AIDS knowledge of pregnant women in India. In a sub-sample of these women, we documented the extent to which they experienced adverse social and physical difficulties within their home. The study was performed at an urban antenatal hospital clinic in Maharastra, India. From April to September 2001, structured interviews were conducted on 707 randomly selected antenatal clinic patients related to HIV/AIDS knowledge. Of these, 283 were further interviewed to document any social or physical difficulties they experienced. Over 75% of women displayed knowledge of primary transmission routes. Nearly 70% of women demonstrated knowledge of maternal to child transmission, however, only 8% knew of any methods of prevention. TV and written material were more strongly related to knowledge than access to radio messages or conversations with individuals. Thirty per cent of the women experienced physical or mental abuse or their spouse's alcohol and/or drug problems. Women reporting such abuse were more than twice as likely to have adequate HIV/AIDS knowledge compared with women reporting no such abuse. We found no relationship between reported household abuse and educational level of woman, husband, occupation of either partner, language or religion. We found no relationship between HIV status and knowledge of HIV and no relationship between HIV status and risk of abuse in the household. However, the total number of HIV patients in our sample was very small.

Women's acceptability and husband's support of rapid HIV testing of pregnant women in India.

This study examined acceptability among pregnant women and their husbands for HIV testing within the antenatal clinic (ANC) and delivery room (DR) of a government hospital in Pune, India from September 2000 to November 2001. Acceptance of HIV counselling and testing was high with 83% of eligible women in the antenatal clinic (851 of 1025) and 68% of eligible women in the delivery room (417 of 613) getting tested on the same day. Structured interviews were conducted on 94 pregnant women in the ANC 50 women in the DR, and 100 husbands who accompanied their wives in the ANC. These data indicated that the majority of women agreed to be tested independently without the need for further consultation with family members, a view that was strongly supported in this sub-sample of accompanying husbands. For delivering women who were not progressing in their labour, counselling in the DR allowed for individual attention to questions and concerns thereby making counselling in the DR feasible.

Sensitivity and specificity of rapid HIV testing of pregnant women in India.

OBJECTIVE: Efforts to prevent HIV transmission from mother to infants in settings like India may benefit from the availability of reliable methods for rapid and simple HIV screening. Data from India on the reliability of rapid HIV test kits are limited and there are no data on the use of rapid HIV tests for screening of pregnant women. METHODS: Pregnant women attending an antenatal clinic and delivery room in Pune agreed to participate in an evaluation of five rapid HIV tests, including (a) a saliva brush test (Oraquick HIV-1/2, Orasure Technologies Inc.), (b) a rapid plasma test (Oraquick HIV-1/2) and (c) three rapid finger prick tests (Oraquick HIV-1/2; HIV-1/2 Determine, Abbott; NEVA HIV-1/2 Cadila). Results of the rapid tests were compared with three commercial plasma enzyme immunoassay (EIA) tests (Innotest HIV AB EIA, Lab systems/ELISCAN HIV AB EIA, UBI HIV Ab EIA). RESULTS: Between September 2000 and October 1, 2001, 1258 pregnant women were screened for HIV using these rapid tests. Forty-four (3.49%) of the specimens were HIV-antibody-positive by at least two plasma EIA tests. All of the rapid HIV tests demonstrated excellent specificity (96-100%). The sensitivity of the rapid tests ranged from 75-94%. The combined sensitivity and specificity of a two-step algorithm for rapid HIV testing was excellent for a number of combinations of the five rapid finger stick tests. CONCLUSION: In this relatively low HIV prevalence population of pregnant women in India, the sensitivity of the rapid HIV tests varied, when compared to a dual EIA algorithm. In general, the specificity of all the rapid tests was excellent, with very few false positive HIV tests. Based upon these data, two different rapid HIV tests for screening pregnant women in India would be highly sensitive, with excellent specificity to reliably prevent inappropriate use of antiretroviral therapy for prevention of vertical HIV transmission.

Fetal hydantoin syndrome with rheumatic valvular heart disease.

Research has shown that anticonvulsants are teratogens and pose a risk for fetal malformations. Though Fetal Hydantoin Syndrome (FHS) was first reported by Langhman and others, wide phenotypic variability of this syndrome has lead many clinicians to question its very existence. We report a twelve year old girl with FHS with rheumatic valvular heart disease.

Asian paralysis syndrome.

We report 20 children admitted to the paediatric ward of a public general hospital for acute flaccid paralysis, which was bilaterally symmetrical in all cases and was associated with bulbar involvement in eight of them. Recovery was partial. Nerve conduction studies showed motor axonal neuropathy. This new disease, variously termed as non-inflammatory neuropathy/Chinese paralysis syndrome must be differentiated from Guillain-Barré syndrome (GBS) and poliomyelitis. Both GBS and Asian paralysis syndrome have bilaterally symmetrical flaccid paralysis but GBS tends to have sensory involvement, full recovery occurs in 90% of cases and nerve conduction shows demyelinating neuropathy. Asian paralysis syndrome and poliomyelitis are pure motor lesions without sensory changes and partial recovery, but poliomyelitis differs in that paralysis is asymmetrical and unequal, muscle spasm is always present in the initial stage and there are prodromal symptoms. Nerve conduction studies show anterior horn cell disease. This new entity, common in Asian populations, assumes public health importance when it mimics poliomyelitis in a country that has tried to eliminate poliomyelitis by universal immunization. To the best of our knowledge, this is the first report of Asian paralysis syndrome in children in our area.

Efficacy of two dose measles vaccination in a community setting.

OBJECTIVE: To compare the efficacy of two dose and single dose measles vaccination in a community setting. DESIGN: Two community ICDS blocks with populations of 8990 and 8550 children below 12 years of age were selected. Block A had 1560 children between 9 mo to 1 year of age and Block B had 1380 children between the age of 9 mo to 1 year. METHODS: All eligible children between 9 mo to 1 year of age were given measles vaccination in October 1994. Only the children in Group A were given a second dose of measles (as MMR) in April 1995; six months after the first dose. A survey was undertaken from January 1996 to April 1996 to clinically evaluate the number of cases of measles in both these blocks. RESULTS: In Block A 3 children developed measles, whereas in Block B, there were 16 cases of measles (p < 0.01). All other parameters in both groups, e.g., cold chain maintenance were similar. CONCLUSION: This study supports the superiority of two dose measles vaccination given at an interval of 6 months over a single dose measles in a community setting.

Immunogenicity study of Haemophilus influenzae type B conjugate vaccine in Indian infants.

OBJECTIVE: To assess the immunogenicity in Indian infants to Haemophilus influenzae b oligosaccharide conjugate vaccine (HbOC). DESIGN: Prospective multicenter study. SETTING: Pediatric Out Patient Department of general hospitals in Pune and Mumbai. SUBJECTS: 124 full term healthy infants brought for routine DPT/OPV immunization. METHODS: Infants were administered 3 doses of 0.5 ml of HbOC, on the same day as their DPT/OPV immunization, injected intramuscularly on the limb opposite to that where DPT vaccine was administered. Data on local reactions and general symptoms was collected for three days after every dose. The children had their blood collected for assay of anti PRP (polyribosil ribitol phosphate) antibody titers, along with the first injection and one month after the third injection. One hundred and three infants completed the study protocol with two blood collections. RESULTS: The initial geometric mean titers (GMT) of 0.124 mcg/ml rose by 37 times to 4.552 mcg/ml. Ninety eight children (95.1%) had a final titer of > or = 0.15 mcg/ml, the minimum level associated with protection, and 77 children (74.8%) had a final level of > or = 1.0 mcg/ml, a level associated with long term protection. CONCLUSION: HbOC is immunogenic in Indian infants when used as per the locally recommended DPT/OPV immunization schedule.