TB-HIV co-infection among pregnant women in Karnataka, South India: a case series

Tuberculosis [TB] is a significant contributor to mortality in HIV-infected patients. Concurrent TB infection is also a significant contributing factor to maternal mortality in human immunodeficiency virus [HIV]-infected pregnant women. Studies addressing the outcomes of TB and HIV co-infection among pregnant women are generally infrequent. Although limited, the records maintained by the Revised National Tuberculosis Control Programme [RNTCP] and the National AIDS Control Programme [NACP] in Karnataka State, Southern India provide information about the numbers of pregnant women who are co-infected with TB and HIV and their pregnancy outcomes. We reviewed the data and conducted this study to understand how TB-HIV co-infection influences the outcomes of pregnancy in this setting. We sought to determine the incidence and treatment and delivery outcomes of TB-HIV co-infected pregnant women in programmatic settings in Karnataka State in southern India. The study participants were all the HIV-infected pregnant women who were screened for tuberculosis under the NACP from 2008 to 2012. For the purposes of this study, the program staff in the field gathered the data regarding on treatment and delivery outcomes of pregnant women. A total of seventeen pregnant women with TB-HIV co-infection were identified among 3,165,729 pregnant women [for an incidence of 5.4 per million pregnancies]. The median age of these pregnant women was 24 years, and majority were primiparous women with WHO HIV stage III disease and were on a stavudine-based ART regimen. The maternal mortality rates were 18% before delivery and 24% after delivery. The abortion rate was 24%, and the neonatal mortality rate was 10%. The anti-tuberculosis treatment and anti-retroviral treatment outcome mortality rates were 30% and 53%, respectively. Although the incidence of TB among the HIV-infected pregnant women was marginally less than that among the non-HIV-infected women, the delivery outcomes were relatively poorer. The current strategy for the management of TB among the HIV-positive pregnant women needs urgent review

Genetic Factors Associated with Slow Progression of HIV among Perinatally-Infected Indian Children.

Objectives: To study the association between common AIDS restriction genes and slow disease progression among perinatally-infected children in India. Methods: ART-naïve children were identified and selected host factors including CCR5-Δ32, SDF1-3’A, CCR5-59029G, HLA-B*27, B*57 were studied using allele-specific PCR-RFLP and SSPGo HLA typing kits. Results: Among 165 children, 10 (6%) long-term non-progressors and 8 (5%) slow progressors were identified. For comparison, 12 children with normal progression of HIV were included. The frequencies of CCR5-Δ32 deletion, SDF1-3’A and CCR5-59029G did not differ significantly. HLA-B*27 and B*57 were observed only in long-term non-progressors or slow progressors, who also harbored either SDF1-3’A and/or CCR5-59029G. Conclusions: There is an association between host genetic factors and slow disease progression in this population.

Dried blood spot HIV-1 RNA quantification: A useful tool for viral load monitoring among HIV-infected individuals in India.

Background & objectives: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log10 copies/ml. Measurable viral load (>3.0 log10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (-0.21 to +0.8 log10 copies/ml). The mean difference was 0.29 log10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting. Interpretation & conclusions: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally.

Intermittent Short Course Therapy for Pediatric Tuberculosis.

We conducted this study to assess the efficacy of intermittent short course therapy in all forms of pediatric tuberculosis using a coordinated approach with Revised National Tuberculosis Control Programme (RNTCP). Sixty-five children were treated using RNTCP protocols with some modifications, such as dose adjustments or prolongation of treatment in selected children. Overall response rate was 95% (pulmonary 94% and extra pulmonary 97%). There was one case with possible relapse. With dynamic inputs from both the treating pediatrician and personnel from Directly Observed Treatment – Short-course (DOTS) centers, we could successfully implement RNTCP protocols in childhood tuberculosis.

Neonatal & maternal group B streptococcal infections: a comprehensive review.

Group B Streptococcus is an important cause of maternal and neonatal morbidity and mortality in many parts of the world. The last two decades have seen intensified efforts in the Western hemisphere in the prevention of this devastating infection by identifying and treating pregnant women who carry group B streptococci or who are at highest risk of transmitting the organism to newborns. The intrapartum use of antibiotics in these women has led unequivocally to a decrease in the rate of neonatal group B streptococcal disease. Although studies in India show a predominance of Gram negative bacterial sepsis among infants, contributing to infant mortality, it is possible that the role of group B Streptococcus has been underestimated. This review discusses its epidemiology in India, and summarizes current concepts of microbiology, pathogenesis, clinical management and preventative issues regarding group B streptococcal disease.

Human immunogenicity studies on group A streptococcal C5a peptidase (SCPA) as a potential vaccine against group A streptococcal infections.

BACKGROUND & OBJECTIVES: Group A streptococcal C5a peptidase (SCPA) is a major virulence surface factor. Its highly conserved nature among all tested serotypes of group A streptococci (GAS) as well as animal protection studies make SCPA a prime vaccine candidate. The present study was undertaken to explore the human immunogenicity to SCPA using an indirect enzyme-linked immunosorbent assay. METHODS: Children (n=72) who had signs and symptoms of acute pharyngitis and had GAS isolated from the throat at initial visit were included. Acute and convalescent sera were collected 4 weeks apart. ELISA was performed using recombinant SCPA peptide as antigen. RESULTS: The mean convalescent anti-SCPA level was twice the level of mean acute anti-SCPA and the difference was statistically significant (P < 0.0001). There was a rise in convalescent anti-SCPA in all children aged 2-12 yr. INTERPRETATION & CONCLUSION: Our observations confirmed that SCPA was highly immunogenic in children infected with group A streptococcal pharyngitis. Further studies need to be done to characterize the immune response including antibody subclass.

Addressing the burden of group A streptococcal disease in India.

Group A streptococcus-associated disease and sequelae continue to have devastating effects on public health and national economy as they mainly affect children and young adults. There is an urgent need for wider application of methods of primary prevention, in the form of optimal diagnosis and management of the simple group A streptococcal sore throat. This review article briefly summarizes the burden of streptococcal disease in India, and discusses treatment options standardized by the World Health Organization. Penicillin continues to remain the drug of choice for treating group A streptococcal pharyngitis and for prevention of acute rheumatic fever in non-allergic patients. Also discussed in this review are contemporary thoughts on streptococcal "carriers", recurrent infections, antibiotic treatment "failures" and emergence of drug resistance among group A streptococci.