Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of Pakistan: a community-based, cluster-randomised trial.

BACKGROUND: Umbilical cord infection (omphalitis) is a risk factor for neonatal sepsis and mortality in low-resource settings where home deliveries are common. We aimed to assess the effect of umbilical-cord cleansing with 4% chlorhexidine (CHX) solution, with or without handwashing with antiseptic soap, on the incidence of omphalitis and neonatal mortality. METHODS: We did a two-by-two factorial, cluster-randomised trial in Dadu, a rural area of Sindh province, Pakistan. Clusters were defined as the population covered by a functional traditional birth attendant (TBA), and were randomly allocated to one of four groups (groups A to D) with a computer-generated random number sequence. Implementation and data collection teams were masked to allocation. Liveborn infants delivered by participating TBAs who received birth kits were eligible for enrolment in the study. One intervention comprised birth kits containing 4% CHX solution for application to the cord at birth by TBAs and once daily by family members for up to 14 days along with soap and educational messages promoting handwashing. One intervention was CHX solution only and another was handwashing only. Standard dry cord care was promoted in the control group. The primary outcomes were incidence of neonatal omphalitis and neonatal mortality. The trial is registered with ClinicalTrials.gov, number NCT00682006. FINDINGS: 187 clusters were randomly allocated to one of the four study groups. Of 9741 newborn babies delivered by participating TBAs, factorial analysis indicated a reduction in risk of omphalitis with CHX application (risk ratio [RR]=0·58, 95% CI 0·41-0·82; p=0·002) but no evidence of an effect of handwashing (RR=0·83, 0·61-1·13; p=0·24). We recorded strong evidence of a reduction in neonatal mortality in neonates who received CHX cleansing (RR=0·62, 95 % CI 0·45-0·85; p=0·003) but no evidence of an effect of handwashing promotion on neonatal mortality (RR=1·08, 0·79-1·48; p=0·62). We recorded no serious adverse events. INTERPRETATION: Application of 4% CHX to the umbilical cord was effective in reducing the risk of omphalitis and neonatal mortality in rural Pakistan. Provision of CHX in birth kits might be a useful strategy for the prevention of neonatal mortality in high-mortality settings. FUNDING: The United States Agency for International Development.

Impact of Treatment with RUTF on Plasma Lipid Profiles of Severely Malnourished Pakistani Children.

(1) Background: Little is known on impacts of ready-to-use therapeutic food (RUTF) treatment on lipid metabolism in children with severe acute malnutrition (SAM). (2) Methods: We analyzed glycerophospholipid fatty acids (FA) and polar lipids in plasma of 41 Pakistani children with SAM before and after 3 months of RUTF treatment using gas chromatography and flow-injection analysis tandem mass spectrometry, respectively. Statistical analysis was performed using univariate, multivariate tests and evaluated for the impact of age, sex, breastfeeding status, hemoglobin, and anthropometry. (3) Results: Essential fatty acid (EFA) depletion at baseline was corrected by RUTF treatment which increased EFA. In addition, long-chain polyunsaturated fatty acids (LC-PUFA) and the ratio of arachidonic acid (AA)/linoleic acid increased reflecting greater EFA conversion to LC-PUFA, whereas Mead acid/AA decreased. Among phospholipids, lysophosphatidylcholines (lyso.PC) were most impacted by treatment; in particular, saturated lyso.PC decreased. Higher child age and breastfeeding were associated with great decrease in total saturated FA (ΣSFA) and lesser decrease in monounsaturated FA and total phosphatidylcholines (ΣPC). Conclusions: RUTF treatment improves EFA deficiency in SAM, appears to enhance EFA conversion to biologically active LC-PUFA, and reduces lipolysis reflected in decreased ΣSFA and saturated lyso.PC. Child age and breastfeeding modify treatment-induced changes in ΣSFA and ΣPC.

Consecutive outbreaks of Vibrio cholerae O139 and V. cholerae O1 cholera in a fishing village near Karachi, Pakistan.

In July 2002 and June 2003, cholera outbreaks were detected by a diarrhoea surveillance system in a village outside Karachi, Pakistan. Specimens were culture confirmed. The first outbreak was caused by Vibrio cholerae O139 (n = 30) and the second outbreak by V. cholerae O1 (n = 39). Demographic and clinical features of patients were recorded and case-control studies were conducted following each outbreak. Clinical information was obtained for 29 of the 30 patients in the first outbreak, and 2 of the patients in the second outbreak were either out of the area or lost to follow-up, leaving 29 and 37 cases in the analysis for the first and second outbreak, respectively. Eighteen (49%) of the 37 V. cholerae O1 patients were under 2 years of age compared with 6 (21%) of the 29 V. cholerae O139 patients (P = 0.02). Vibrio cholerae O139-infected patients were more likely to be febrile (16/29) than those infected with V. cholerae O1 (2/37; P<0.001). A household contact with cholera was a risk factor in both outbreaks; water source was a risk factor in the first outbreak only. Geographically, cases were clustered during the first outbreak but not during the second. Person-to-person contact and water reservoirs appear to be the main transmission routes for cholera in this setting.

A comparison of disease caused by Shigella and Campylobacter species: 24 months community based surveillance in 4 slums of Karachi, Pakistan.

Despite the efforts of the international community diarrheal diseases still pose a major threat to children in children less than five years of age. Bacterial diarrhea has also emerged as a public health concern due to the proliferation of drug resistant species in many parts of the world. There is a paucity of population-based data about the incidence of shigellosis and Campylobacter infections in Pakistan. We report country specific results for Shigella diarrhea that were derived from a multicenter study conducted in six Asian countries. Disease surveillance was conducted over a 24 month period in urban slums of Karachi, Pakistan, a city with a population of 59,584. Cases were detected through passive detection in study treatment centers. Stool specimens or rectal swabs were collected from all consenting patients. Between January 2002 and December 2003 10,540 enteric infection cases were detected. The incidence rate of treated diarrhea in children under 5 was 488/1000/year. In children, 5 years and older, the diarrhea rate was 22/1000/year. 576 (7%) Campylobacter isolates were detected. The pre-dominant Campylobacter species was C. jenuni with an increase of 29/1000 year in children under 5 years. Shigella species were isolated from 394 of 8032 children under 5 years of age. Shigella flexneri was the dominant species (10/1000/year in children under 5 years) followed by Shigella sonnei (3.9/1000/year), Shigella boydii (2.0/1000/year) and Shigella dysenteriae (1.3/1000/year). Shigellosis and Campylobacter infection rates peaked during the second year of life. The incidence rate of shigellosis increased in old age but such a trend was not observed in Campylobacter infections. Of 394 shigellosis patients 123 (31%) presented with dysentery in contrast to only 54 (9%) of 576 patients with Campylobacter infections (p<0.001). Both Campylobacter infections and shigellosis are common in community settings of Pakistan but shigellosis presented more frequently with abdominal pain and dysentery than Campylobacter infections indicating that shigellosis may be a more severe illness than Campylobacter infections. Due to the increased and disease severity, drug resistant shigella have become a significant health problem; moreover it is a disease of poor and impoverished people who do not have the access to standard water and sanitary conditions, health care services or optimal treatment. In the face of these facts it is empirically important to develop a low cost effective vaccine that can protect these populations for a longer duration.

Frequency of isolation of various subtypes and antimicrobial resistance of Shigella from urban slums of Karachi, Pakistan.

OBJECTIVES: Shigellosis remains a major public health problem in developing countries. Antimicrobial resistance has complicated the empirical treatment. Knowledge of serotypes is crucial in vaccine development, as cross-protection between various serotypes is limited. Therefore we conducted a prospective study to determine the frequency of isolation of Shigella serotypes and antimicrobial resistance. METHODS: Stool samples from 8155 individuals, collected through a surveillance study conducted in four slums of Karachi from January 2002 to March 2004, were cultured. RESULTS: Shigella was isolated in 394 (4.8%) of 8155 patients presenting with diarrhea. Two hundred and forty-two (62%) isolates were Shigella flexneri, 72 (18%) were Shigella sonnei, 43 (11%) were Shigella boydii, and 37 (9%) were Shigella dysenteriae. Thirteen S. flexneri serotypes were identified, of which the most frequent were 2a (38), 6 (37), and 1b (25), followed by 2b (23). Only 22 (5.6%) Shigella isolates were found to be pan-susceptible. Large proportions of isolates were resistant to co-trimoxazole (89% S. flexneri, 81% S. dysenteriae, 80% S. sonnei, and 56% S. boydii) and ampicillin (87% S. flexneri, 68% S. dysenteriae, 35% S. boydii, and 4% S. sonnei). CONCLUSIONS: Concurrent circulation of multiple strains with high resistance is worrying and mandates surveillance at the national level to facilitate the control of shigellosis.

Lessons and implications from a mass immunization campaign in squatter settlements of Karachi, Pakistan: an experience from a cluster-randomized double-blinded vaccine trial [NCT00125047].

OBJECTIVE: To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. METHODS: A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. RESULTS: The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial when the code is broken. Throughout the vaccination campaign safe injection practices were maintained and the cold chain was not interrupted. Mass vaccination in slums had good acceptance. Because populations in such areas are highly mobile, settlement conditions could affect coverage. Systemic reactions were uncommon and local reactions were mild and transient. Close community involvement was pivotal for information dissemination and immunization coverage. CONCLUSION: This vaccine strategy described together with other information that will soon be available in the area (cost/effectiveness, vaccine delivery costs, etc) will make typhoid fever control become a reality in the near future.