Effect of preconception multiple micronutrients vs. iron-folic acid supplementation on maternal and birth outcomes among women from developing countries: a systematic review and meta-analysis.

Background: Maternal malnutrition affects the somatic growth of the fetus and subsequent adverse events during infancy and childhood period. Though trials have been conducted on multiple micronutrient (MMN) supplements initiated during the preconception period, there is no collated evidence on this. Materials and methods: We performed a systematic review of published trials with the application of Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The searches were conducted until 30 September 2023. Meta-analysis was performed using Review Manager 5 software. The primary objective was to compare the effect of preconception MMN vs. iron-folic acid (IFA) supplementation on newborn anthropometric parameters at birth. Results: Of the 11,832 total citations retrieved, 12 studies with data from 11,391 participants [Intervention = 5,767; Control = 5,624] were included. For the primary outcome, there was no significant difference in the birth weight [MD, 35.61 (95% CI, -7.83 to 79.06), p = 0.11], birth length [MD, 0.19 (95% CI, -0.03 to 0.42), p = 0.09], and head circumference [MD, -0.25 (95% CI, -0.64 to -0.14), p = 0.22] between the MMN and control groups. For all the secondary outcomes [except for small for gestational age (SGA) and low birth weight (LBW)], the difference between the MMN and control groups was not significant. The GRADE evidence generated for all the outcomes varied from "very low to moderate certainty." Conclusion: A "very low certainty" of evidence suggests that MMN supplementation may not be better than routine IFA supplementation in improving newborn anthropometric parameters (weight, length, and head circumference). The adverse events resulting from the supplementation were not significant. We need better quality uniformly designed RCTs before any firm recommendation can be made.Systematic review registration: identifier (CRD42019144878: https://www.crd.york.ac.uk/prospero/#searchadvanced).

Prevalence and Pattern of Morbidity, Febrile Illness, and Treatment-Seeking Behavior in a Tribal-Dominated District in Odisha, India: An Observational Study.

Background Tribal populations constitute a major portion of India's total population, especially in the eastern and northeastern states. We lack comprehensive information on the community burden of general morbidity and febrile illness in tribal population-dominated areas, which is quite essential for the microplanning of healthcare expenditure and implementation. This study aimed to provide evidence on the prevalence and pattern of general morbidity and febrile illness at the community level as well as the treatment-seeking behaviour in a tribal-dominated area. Methods The study was undertaken as an observational study in the community setting; looking into seasonal cross-sectional evidence on period prevalence (two weeks) of morbidity and qualitative/semiquantitative information on treatment-seeking behaviour of the selected community during 2012 and 2013. Result This study involved 5541, 5482, and 5638 individuals during the rainy season 2012, winter 2012-13, and rainy season 2013 seasons, respectively, from 25 tribal villages of Odisha, India. A period prevalence (two weeks) of overall morbidities was shown to be 27.28% and 28.9% during the rainy seasons of 2012 and 2013, respectively, of which 13% and 11.5%, respectively, were febrile, with low prevalence (6.44% overall morbidity and 1.81% febrile illness) in the winter of 2012-13. It indicated inadequacy in skills of the village-level health staff, monitoring of supplies/logistics, and population awareness for early reporting of fever to healthcare providers at the community level. Conclusion The evidence provided by the study would be helpful in making public health plans in tribal settings and also highlighted the opportunity to improve tribal health status through community awareness, especially in areas and populations with limited health access.

Active Pharmacovigilance for Primaquine Radical Cure of Plasmodium vivax Malaria in Odisha, India.

Plasmodium vivax malaria elimination requires radical cure with chloroquine/primaquine. However, primaquine causes hemolysis in glucose-6-phosphate dehydrogenase-deficient (G6PDd) individuals. Between February 2016 and July 2017 in Odisha State, India, a prospective, observational, active pharmacovigilance study assessed the hematologic safety of directly observed 25 mg/kg chloroquine over 3 days plus primaquine 0.25 mg/kg/day for 14 days in 100 P. vivax patients (≥ 1 year old) with hemoglobin (Hb) ≥ 7 g/dL. Pretreatment G6PDd screening was not done, but patients were advised on hemolysis signs and symptoms using a visual aid. For evaluable patients, the mean absolute change in Hb between day 0 and day 7 was -0.62 g/dL (95% confidence interval [CI]: -0.93, -0.31) for males (N = 53) versus -0.24 g/dL (95%CI: -0.59, 0.10) for females (N = 45; P = 0.034). Hemoglobin declines ≥ 3 g/dL occurred in 5/99 (5.1%) patients (three males, two females); none had concurrent clinical symptoms of hemolysis. Based on G6PD qualitative testing after study completion, three had a G6PD-normal phenotype, one female was confirmed by genotyping as G6PDd heterozygous, and one male had an unknown phenotype. A G6PDd prevalence survey was conducted between August 2017 and March 2018 in the same region using qualitative G6PD testing, confirmed by genotyping. G6PDd prevalence was 12.0% (14/117) in tribal versus 3.1% (16/509) in nontribal populations, with G6PD Orissa identified in 29/30 (96.7%) of G6PDd samples. Following chloroquine/primaquine, notable Hb declines were observed in this population that were not recognized by patients based on clinical signs and symptoms.

Molecular epidemiology of hepatitis B virus in primitive tribes of Odisha, eastern India.

BACKGROUND AND OBJECTIVE: Among the indigenous population of India, Primitive Tribal Groups (PTGs) are vulnerable to various health related events and some of the PTGs are showing a decline in population associated with high mortality rates. The present study was undertaken to define the prevalence of Hepatitis B Virus (HBV) infection, its genetic characterization and possible risk factors for transmission in five PTGs in Odisha, India. METHODS: Cross-sectional observational studies were carried out in the Lodha, Saora, Khadia, Mankidia, and Juanga tribes residing in different parts of Odisha between 2006 and 2010. RESULTS: Hepatitis B surface antigen (HBsAg) prevalence was 0.8%, 0.9%, 0.9%, 3.7%, and 1.7% in Lodha, Saora, Khadia, Mankidia, and Juanga tribes, respectively. While 54.8% of seropositive (HBsAg) cases demonstrated HBV DNA, occult HBV infection was observed in 19.48% of cases. High viral load with detectable 'e' antigen was found in 29% of HBsAg-positive individuals. All HBV isolates (n=17) were genotype D without pre-core mutants. Only 15.6% of HBV positive individuals had symptoms of hepatic disease, though none had severe manifestations. Multivariate analysis of the prevailing risk factors indicated that shaving by the village barber was significantly associated with HBV transmission in males. Tattooing was found to be significantly associated with females. INTERPRETATION AND CONCLUSION: This is the first report on HBV infection in PTGs of Odisha that suggests a high potential for transmission of HBV infection in two PTGs (Mankidia and Juanga). It warrants early public health attention in tribal populations vulnerable to HBV infection.

Etoposide-induced cytogenotoxicity in mouse spermatogonia and its potential transmission.

As cancer chemotherapeutic agents are cytogenotoxic but not target-specific during systemic treatment, they affect all the encountered cells including the non-cancerous ones and consequently lead to the recurrence of second malignancy in post-chemotherapeutic cancer survivors. The effects would be persistent if the stem cells were affected. These drugs also may affect germline cells during therapeutic treatments. There is every chance that the effects are transmitted through the germline cells to the gametes and to the next generation if the gonadal mother cells are affected. Such transmission of effects from the post-chemotherapeutic childhood cancer survivors is of serious concern but very little attention has been given so far to such studies. Etoposide (VP-16)--a semi-synthetic epipodophyllotoxin derivative, a DNA non-intercalating agent and a topoisomerase II inhibitor--is prescribed frequently for the treatment of various types of cancers. It is a potent clastogen inducing chromosomal damage both in vitro and in vivo. Its clastogenic effect is indirect through inhibition of the catalytic activity of topoisomerase II enzymes, which maintain the topology of DNA during replication, recombination, transcription, etc. by forming a 'cleavable complex' and facilitate the cleaving and re-ligation of the cleaved DNA to relieve the torsional stress during such events. Transient stabilization of the cleavable complex by etoposide leads to illegitimate ligation of the cleaved DNA. Consequently, single- and double-strand breaks occur. In the present study, the clastogenic potential of three different doses of etoposide (10, 15 and 20 mg kg(-1)) in the male germline of mice was assessed from the dividing spermatogonia after a single exposure for one cell cycle duration at 24 h post-treatment. Transmission of such effects was assessed from the frequency of aberrant primary spermatocytes at week 4 post-treatment and of abnormal sperm at week 8 post-treatment. All three doses of etoposide were found to be clastogenic to the dividing spermatogonia of mice, and mostly chromatid breaks were induced. The effects also were transmitted through the male germline of mice, which was evident from the prevalence of statistically significant increased percentages of aberrant primary spermatocytes at week 4 posttreatment and the higher percentages of abnormal sperm at week 8 post-treatment. Thus, there is every chance that the cytogenotoxic effects of etoposide are transmitted to the next generation through the male germline of post-chemotherapeutic cancer survivors, therefore it is essential to make etoposide target-specific or modulate its effects.

Cytogenetic risk assessment of etoposide from mouse bone marrow.

Increased clinical applications of the anticancer drug etoposide (a non-intercalative epipodophyllotoxin derivative) and the frequent induction of a second malignancy, particularly leukaemia, in post-etoposide-treated cancer survivors warrant detailed genotoxicity testing of etoposide. The genotoxicity test results available on etoposide are either primarily in in vitro test systems or in lower organisms after treatment with unusually high doses, or after chronic exposures, having little extrapolative value to humans. Therefore, a cytogenetic risk assessment study on etoposide in mouse in vivo was undertaken after a low dose (in accordance with the human therapeutic dose) single exposure. The cytogenetic toxicity of etoposide was assessed from bone marrow of mouse at three separate endpoints: chromosomal aberration and mitotic index studies at 24 h post-treatment and the micronucleus test (MNT) at 30 h post-treatment. The flame drying technique using colchicine, hypotonic sodium citrate, methanol-glacial acetic acid and Giemsa was followed for the preparation of slides for the metaphase chromosomal aberration and mitotic index studies and a simple technique was followed for the MNT. Although induction of chromosomal aberrations, excluding gaps, per 100 metaphases by 10 and 15 mg kg(-1) etoposide was not significant statistically, 20 mg kg(-1) of etoposide induced a significantly higher number of chromosomal aberrations in female (P < or = 0.01) and male (P < or = 0.05) mice. There was no significant change in the induced percentages of dividing cells by any of the doses of etoposide tested. The micronucleus induction also was not significant statistically with the lowest dose but it was significant in female (P