Shazia Sultana

Community-based Treatment of Serious Bacterial Infections in Newborns and Young Infants A Randomized Controlled Trial Assessing Three Antibiotic Regimens

Background: Sepsis in the neonatal period is a major cause of child mortality in low-income countries. Hospitalization and parenteral penicillin/ampicillin and gentamicin therapy are recommended for management. Many families, however, are unable to access hospital care, and most home-delivered newborns who develop sepsis die without receiving antibiotic therapy. Appropriate community-based therapy in such situations is undefined. We compared failure rates of 3 clinic-based antibiotic regimens in 0- to 59-day-old infants with possible serious bacterial infection whose families refused hospitalization in Karachi communities with high neonatal mortality rates >45/1000 live births. Methods: Eligible infants were randomly assigned to 7 days of: (1) procaine penicillin [50,000 units/kg once daily (OD) by intramuscular injection (IM)] and gentamicin (5 mg/kg OD IM) reference arm, (2) ceftriaxone (50 mg/kg OD IM), or (3) oral trimethoprim-sulfamethoxazole (TMP-SMX) at 10 mg/kg/day divided twice daily and gentamicin IM OD. Primary outcome was treatment failure, defined as death, deterioration in clinical condition during therapy or no improvement after 2 days. Results: Possible serious bacterial infection was diagnosed in 704 infants, among 5766 screened. Among 434 (61.6%) randomized to clinic-based therapy, there were 13 of 145 failures with penicillin-gentamicin, 22 of 145 with ceftriaxone and 26 of 143 with TMP-SMX-gentamicin. Treatment failure was significantly higher with TMP-SMX-gentamicin compared with penicillin-gentamicin [relative risk 2.03, 95% confidence interval: 1.09 – 3.79] by intention-to-treat analysis. Differences were not significant in the ceftriaxone versus penicillin-gentamicin comparison [relative risk 1.69, 95% confidence interval 0.89–3.23). By 14 days, there were 2 deaths in the penicillin-gentamicin group, 3 in the ceftriaxone group and 11 in the TMP-SMX-gentamicin group [relative risk 5.58, 95% confidence interval: 1.26–24.72 (group 3 versus 1)]. Conclusion: When hospitalization of sick infants is unfeasible, outpatient therapy with injectable antibiotics is an effective option. Procaine penicillin-gentamicin was superior to TMP-SMX-gentamicin. Ceftriaxone is a more expensive option, and may be less effective, although this requires further research.

Why do families of sick newborns accept hospital care? a community-based cohort study in Karachi, Pakistan

Objective:Sick young infants are at high risk of mortality in developing countries, but families often decline hospital referral. Our objective was to identify the predictors of acceptance of referral for hospital care among families of severely ill newborns and infants <59 days old in three low-income communities of Karachi, Pakistan.Study Design:A cohort of 541 newborns and infants referred from home by community health workers conducting household surveillance, and diagnosed with a serious illness at local community clinics between 1 January and 31 December 2007, was followed-up within 1 month of referral to the public hospital.Result:Only 24% of families accepted hospital referral. Major reasons for refusal were financial difficulties (67%) and father/elder denying permission (65%). Religious/cultural beliefs were cited by 20% of families. Referral acceptance was higher with recognition of severity of the illness by mother (odds ratio=12.7; 95% confidence interval=4.6 to 35.2), familys ability to speak the dominant language at hospital (odds ratio=2.0; 95% confidence interval=1.3-3.1), presence of grunting in the infant (odds ratio=3.3; 95% confidence interval=1.2-9.0) and infant temperature <35.5 °C (odds ratio=4.1; 95% confidence interval=2.3 to 7.4). No gender differential was observed.Conclusion:Refusal of hospital referral for sick young infants is very common. Interventions that encourage appropriate care seeking, as well as community-based management of young infant illnesses when referral is not feasible are needed to improve neonatal survival in low-income countries.

Population-based surveillance for severe rotavirus gastroenteritis in children in Karachi, Pakistan

The incidence of rotavirus-associated severe diarrhoea and distribution of rotavirus genotypes in children less than five years of age was determined in two low-income communities in Karachi, Pakistan. Over a two-year period, 717 children met eligibility criteria for severe diarrhoea and stools were obtained from 575 (80%) with 97 (17%) being rotavirus positive. Adjusted annual rates of severe rotavirus diarrhoea in children less than five years and less than one year were respectively 5.7 and 16.9 per 1000 in community A, and 8.1 and 25.4 per 1000 child years of observation in community B. An estimated 1 in 40 infants experience a severe episode of rotavirus gastroenteritis annually in Pakistan. The most common rotavirus strains were G9P[8] (15%), G1P[8] (13%) and G1[P4] (8.4%). This information will inform policy decisions about the introduction of rotavirus vaccines.

Simplified Antibiotic Regimens for the Management of Clinically Diagnosed Severe Infections in Newborns and Young Infants in First-level Facilities in Karachi, Pakistan: Study Design for an Outpatient Randomized Controlled Equivalence Trial

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Incidence of pneumonia, bacteremia, and invasive pneumococcal disease in Pakistani children

Objective  To determine the incidence of pneumonia, bacteremia, and invasive pneumococcal disease (IPD) in Pakistani children <5 years old.

Controlled Evaluation of Bactec Peds Plus/F and Bactec Lytic/10 Anaerobic/F Media for Isolation of Salmonella enterica Serovars Typhi and Paratyphi A from Blood

ABSTRACT We compared anaerobic lytic (AL) and pediatric aerobic resin-containing (Peds Plus/F) blood culture media for the isolation of Salmonella enterica serotype Typhi or Paratyphi A from children. The yields from AL and Peds Plus/F media were the same with equal volumes of blood, but recovery was faster from AL medium than Peds Plus/F medium (10.7 and 16.4 h, respectively) (P < 0.001).

Influenza vaccine acceptance among pregnant women in urban slum areas, Karachi, Pakistan.

BACKGROUND Facilitators and barriers to influenza vaccination among pregnant women in the developing world are poorly understood, particularly in South Asia. We assessed intention to accept influenza vaccine among ethnically diverse low-income pregnant women in Pakistan. METHODS From May to August 2013, we conducted a cross-sectional survey of pregnant women who visited health centers in urban slums in Karachi city. We assessed intention to accept influenza vaccine against socio-demographic factors, vaccination history, vaccine recommendation sources, and other factors. RESULTS In an unvaccinated study population of 283 respondents, 87% were willing to accept the vaccine, if offered. All except two participants were aware of symptoms typically associated with influenza. Perceived vaccine safety, efficacy, and disease susceptibility were significantly associated with intention to accept influenza vaccine (p<0.05). Regardless of intention to accept influenza vaccine, 96% rated healthcare providers as highly reliable source of vaccine information. While a recommendation from a physician was critical for influenza vaccine acceptance, parents-in-law and husbands were often considered the primary decision-makers for pregnant women seeking healthcare including vaccination. CONCLUSIONS Maternal influenza vaccination initiatives in South Asia should strongly consider counseling of key familial decision-makers and inclusion of healthcare providers to help implement new vaccination programs.

Implementation of the ANISA Study in Karachi, Pakistan: Challenges and Solutions.

Background: Aetiology of Neonatal Infection in South Asia (ANISA) is a multicenter study in Bangladesh, India and Pakistan exploring the incidence and etiology of neonatal infections. A periurban site in Karachi was selected for its representativeness of the general population in neonatal health indicators. An established demographic surveillance system and other infrastructure needed for conducting the study already existed at this site. ANISA presents a unique challenge because of the need to capture every birth outcome in the community within a few hours of delivery to reliably estimate the incidence and etiology of early-onset sepsis in a setting where home births and deaths are common. Contextual Challenges: Major challenges at the Karachi site are related to early birth reporting and newborn assessment for births outside the catchment areas, parental refusal to participate, diverse ethnicity of the population, collection of biological specimens from healthy controls, political instability and crime, power outages and blood culture contamination. Some of the remedial actions taken include prolonging working hours; developing counseling skills of field workers; hiring staff with different linguistic abilities from within the study community; liaising with health facilities, key community informants, Lady Health Workers and traditional birth attendants; hiring community mobilizers; enhancing community sensitization; developing contingency plans for field work interruptions and procuring backup generators. The specimen contamination rate has decreased through training, supervision and video monitoring of blood collection procedures with individualized counseling of phlebotomists. Conclusion: ANISA offers lessons for successful implementation of complex study protocols in areas of high child mortality and challenging social environments.

Intention to accept pertussis vaccine among pregnant women in Karachi, Pakistan

BACKGROUND Maternal immunization against pertussis is a potential strategy to protect young infants from severe disease. We assessed factors associated with intention to accept pertussis vaccination among pregnant women in Karachi, Pakistan. METHODS We conducted a cross-sectional survey between May and August 2013 in pregnant women who visited healthcare centers in urban slums of Karachi city. Women completed a survey examining socio-demographic factors, vaccination history, knowledge on pertussis disease, perception of vaccine recommendation sources, and potential influences on vaccine decision-making. RESULTS Of the 283 participants, 259 (92%) provided their intention to either accept or decline pertussis vaccination. Eighty-three percent women were willing to accept the pertussis vaccine if offered during pregnancy. About half (53%) of the participants had ever heard of pertussis disease. Perceptions of pertussis vaccine efficacy, safety, and disease susceptibility were strongly associated with intention to accept pertussis vaccine (p<0.01). Healthcare providers, Ministry of Health, and mass media were considered as highly reliable sources of vaccine recommendation and associated with intention to accept antenatal pertussis vaccination (p<0.001). Healthcare provider recommendation was a common reason cited by respondents for pregnant women to accept antenatal pertussis vaccination (p=0.0005). However, opinion of primary decision-makers in the family (husbands and in-laws) was a crucial reason cited by respondents for pregnant women to reject pertussis vaccination in pregnancy (p=0.003). CONCLUSION Antenatal pertussis vaccination initiatives in South Asia should strongly consider inclusion of family members, healthcare providers, national health ministries, and mass media to help implement new vaccination programs.

A retrospective study of laboratory-based enteric fever surveillance, Pakistan, 2012-2014

2% of blood cultures performed at Aga Khan University Pakistan was positive for enteric fever during 2012–2014. Resistance to fluoroquinolone >90%, cephalosporin <0.1%, and multidrug resistance 52% (Salmonella Typhi) and 2% (Salmonella Paratyphi). Leukopenia, thrombocytopenia, and encephalopathy were common complications among hospitalized cases.