Increasing facility delivery through maternity waiting homes for women living far from a health facility in rural Zambia: a quasi-experimental study.

OBJECTIVE: To report on the effectiveness of a standardised core Maternity Waiting Home (MWH) model to increase facility deliveries among women living >10 km from a health facility. DESIGN: Quasi-experimental design with partial randomisation at the cluster level. SETTING: Seven rural districts in Zambia. POPULATION: Women delivering at 40 health facilities between June 2016 and August 2018. METHODS: Twenty intervention and 20 comparison sites were used to test whether MWHs increased facility delivery for women living in rural Zambia. Difference-in-differences (DID) methodology was used to examine the effectiveness of the core MWH model on our identified outcomes. MAIN OUTCOME MEASURES: Differences in the change from baseline to study period in the percentage of women living >10 km from a health facility who: (1) delivered at the health facility, (2) attended a postnatal care (PNC) visit and (3) were referred to a higher-level health facility between intervention and comparison group. RESULTS: We detected a significant difference in the percentage of deliveries at intervention facilities with the core MWH model for all women living >10 km away (DID 4.2%, 95% CI 0.6-7.6, P = 0.03), adolescent women (<18 years) living >10 km away (DID 18.1%, 95% CI 6.3-29.8, P = 0.002) and primigravida women living >10 km away (DID 9.3%, 95% CI 2.4-16.4, P = 0.01) and for women attending the first PNC visit (DID 17.8%, 95% CI 7.7-28, P < 0.001). CONCLUSION: The core MWH model was successful in increasing rates of facility delivery for women living >10 km from a healthcare facility, including adolescent women and primigravidas and attendance at the first PNC visit. TWEETABLE ABSTRACT: A core MWH model increased facility delivery for women living >10 km from a health facility including adolescents and primigravidas in Zambia.

Linkage between sexual orientation and chromosome Xq28 in males but not in females.

We have extended our analysis of the role of the long arm of the X chromosome (Xq28) in sexual orientation by DNA linkage analyses of two newly ascertained series of families that contained either two gay brothers or two lesbian sisters as well as heterosexual siblings. Linkage between the Xq28 markers and sexual orientation was detected for the gay male families but not for the lesbian families or for families that failed to meet defined inclusion criteria for the study of sex-linked sexual orientation. Our results corroborate the previously reported linkage between Xq28 and male homosexuality in selected kinships and suggest that this region contains a locus that influences individual variations in sexual orientation in men but not in women.

Clinical manifestations and outcome in HIV-infected young infants presenting with acute illness in Durban, South Africa.

OBJECTIVES: In young infants, early development of symptomatic HIV infection increases the risk of morbidity and mortality. A prospective study was conducted over a 1-year period in a region with a high burden of HIV in order to describe the clinical presentation of HIV infection in infants aged between 0 and 59 days on attendance at hospital and the factors associated with the need for urgent hospital management. METHODS: Sick young infants presenting to the King Edward VIII Hospital, Durban between February 2003 and January 2004 were enrolled. After systematic evaluation by a primary health worker, an experienced paediatrician determined the primary diagnosis and need for urgent hospital management. Comparisons of these assessments were stratified by HIV status. Children were classified as HIV-uninfected (HIV ELISA-negative), HIV-exposed-but-uninfected (HIV ELISA-positive and HIV RNA PCR-negative), HIV-infected (HIV ELISA-positive and HIV viral load >400 copies/ml). RESULTS: Of 925 infants enrolled, 652 (70·5%) had their HIV status determined: 70 (10·7%) were HIV-infected, 271 (41·6%) HIV-exposed-but-uninfected, and 311 (47·7%) HIV-uninfected. Factors associated with an increased probability of being HIV-infected included if the mother had children from more than one sexual partner, if the infant had had contact with a tuberculosis-infected person or if the HIV-infected mother and/or her exposed infant failed to receive nevirapine prophylaxis. Signs of severe illness were more frequently encountered in HIV-infected than in HIV-exposed-but-uninfected infants, including the prevalence of chest in-drawing (20·3% vs 8·8%, p = 0·004) and severe skin pustules (18·6% vs 8·6%, p = 0·01). Among infants requiring urgent hospital management, observed or reported feeding difficulties and severe skin pustules were more common in HIV-infected than uninfected infants. More HIV-infected infants (12·9%) required hospitalisation than those who were HIV-exposed-but-uninfected (7·7%) or uninfected (7·4%). Primary diagnoses of pneumonia, sepsis or oral thrush were more frequently seen in HIV-infected than exposed-but-uninfected or HIV-uninfected children. CONCLUSION: Early recognition and triaging of infants suspected of having HIV infection provides an opportunity for early diagnosis and treatment which could prevent the adverse impact of rapidly progressive HIV disease.

Impact of chlorhexidine baths on suspected sepsis and bloodstream infections in hospitalized neonates in Zambia.

INTRODUCTION: Sepsis is the leading cause of infectious morbidity and mortality among hospitalized neonates. In high-resource pediatric and adult intensive care units, use of aqueous chlorhexidine (CHG) solution has been associated with reduced risk of bloodstream infections (BSI). OBJECTIVES: To assess the impact of bathing of neonates with 2% CHG on BSI, suspected sepsis, and mortality in a low-income country neonatal care unit. METHODS: We conducted a secondary analysis of data from the Sepsis Prevention in Neonates in Zambia (SPINZ) study, a prospective observational cohort study performed at a large public referral hospital in Lusaka, Zambia. The SPINZ study assessed the impact of an infection control bundle (consisting of alcohol hand rub, SMS hygiene reminders, enhanced environmental cleaning, and CHG baths for babies ≥1.5 kg) on sepsis, BSI, and all-cause mortality. Episodic shortages in study staffing resulted in some enrolled babies not receiving a CHG bath. Using Longitudinal Targeted Maximum Likelihood Estimation and Cox proportional hazards regression to adjust for observed confounding, we estimated the causal effect of receiving a CHG bath within the first 3 days of life on suspected sepsis, BSI, and death among inborn babies enrolled during the study implementation and intervention phases. RESULTS: The majority of inborn, enrolled babies ≥1.5 kg received a CHG bath within 3 days of NICU admission (864 of 1233, 70%). We found that CHG bathing reduced the hazard rate of BSI among inborn babies ≥1.5 kg by a factor of 0.58 (p = 0.10, 95% CI: 0.31, 1.11), corresponding to an absolute risk reduction of 9.6 percentage points within a week of admission (p = 0.002, 95% CI: 3.4-15.7 percentage points). We did not find a statistically significant effect of CHG bathing on culture-negative sepsis (p = 0.54) or death (p = 0.85). CONCLUSION: In our single center study, CHG bathing at admission was associated with a reduced risk of BSI due to a pathogenic organism after adjusting for potential confounding. Our results suggest that CHG may be an effective intervention for preventing neonatal sepsis in high-risk, low-income country settings.

Interbacterial transfer of Escherichia coli--Drosophila melanogaster Recombinant plasmids.

Recombinants were constructed between various Escherichia coli plasmids and fragments of Drosophila melanogaster DNA. These recombinant plasmids are nonconjugative, but can be mobilized from one cell to another by conjugative sex factors. Of 47 recombinants studied, 46 were mobilized at approximately the same or slightly lower frequencies than the parental plasmids, whereas one was mobilized 1000 times less efficiently.

Regulation in vitro of metallothionein gene binding factors.

Mouse nuclear factors that bind to an upstream metal regulatory element of the mouse metallothionein-I gene have been identified by DNA footprinting and oligonucleotide band shift assays. The formation of complexes at this site can be activated 20- to 40-fold by the vitro addition of ionic cadmium. The activation reaction is rapid, reversible by a metal chelator, and may involve multiple proteins. These results suggest that the initial step in cadmium detoxification is an interaction between the metal and nuclear DNA-binding factors leading to an increase in metallothionein gene transcription. The ability to observe metal activation in vitro makes this a powerful system to study the biochemistry of eukaryotic gene regulation.

Chromosomal location of human metallothionein genes: implications for Menkes' disease.

Human metallothioneins are encoded by a complex multigene family. The chromosomal location of these genes has been determined by gel transfer hybridization analysis of the DNA from human-rodent cell hybrids. Chromosome 16 contains a cluster of metallothionein sequences, including two functional metallothionein I genes and a functional metallothionein II gene. The remaining sequences, including a processed pseudogene, are dispersed to at least four other autosomes. The absence of metallothionein sequences from the X chromosome indicates that Menkes' disease, an X-linked disorder of copper metabolism, affects metallothionein expression by a trans-acting mechanism.

Mammalian metallothionein is functional in yeast.

Expression of two monkey metallothioneins in yeast leads to complementation of both known functions of the endogenous yeast copperthionein gene, namely copper detoxification and autoregulation of transcription. The metallothionein-like proteins of higher and lower eukaryotes are therefore functionally analogous despite their dissimilar primary sequences.

Function and autoregulation of yeast copperthionein.

The CUP1 gene of yeast encodes a small, metallothionein-like protein that binds to and is inducible by copper. A gene replacement experiment shows that this protein protects cells against copper poisoning but is dispensable for normal cellular growth and development throughout the yeast life cycle. The transcription of CUP1 is negatively autoregulated. This feedback mechanism, which is mediated through upstream control sequences, may play an important role in heavy metal homeostasis.

A linkage between DNA markers on the X chromosome and male sexual orientation.

The role of genetics in male sexual orientation was investigated by pedigree and linkage analyses on 114 families of homosexual men. Increased rates of same-sex orientation were found in the maternal uncles and male cousins of these subjects, but not in their fathers or paternal relatives, suggesting the possibility of sex-linked transmission in a portion of the population. DNA linkage analysis of a selected group of 40 families in which there were two gay brothers and no indication of nonmaternal transmission revealed a correlation between homosexual orientation and the inheritance of polymorphic markers on the X chromosome in approximately 64 percent of the sib-pairs tested. The linkage to markers on Xq28, the subtelomeric region of the long arm of the sex chromosome, had a multipoint lod score of 4.0 (P = 10(-5), indicating a statistical confidence level of more than 99 percent that at least one subtype of male sexual orientation is genetically influenced.

Cloning of cauliflower mosaic virus (CLMV) DNA in Escherichia coli.

A plasmid containing cauliflower mosaic virus DNA can be faithfully cloned in Escherichia coli, but proved to be noninfective in test plants.

Overexpression of metallothionein confers resistance to anticancer drugs.

Resistance to antineoplastic agents is the major obstacle to curative therapy of cancer. Tumor cell lines with acquired resistance to the antineoplastic agent cis-diamminedichloroplatinum(II) overexpressed metallothionein and demonstrated cross-resistance to alkylating agents such as chlorambucil and melphalan. Human carcinoma cells that maintained high levels of metallothionein because of chronic exposure to heavy metals were resistant to cis-diamminedichloroplatinum(II), melphalan, and chlorambucil. Furthermore, cells transfected with bovine papilloma virus expression vectors containing DNA encoding human metallothionein-IIA were resistant to cis-diamminedichloroplatinum(II), melphalan, and chlorambucil but not to 5-fluorouracil or vincristine. Thus, overexpression of metallothionein represents one mechanism of resistance to a subset of clinically important anticancer drugs.

Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.

Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.

Effect of presumptive co-trimoxazole prophylaxis on pneumococcal colonization rates, seroepidemiology and antibiotic resistance in Zambian infants: a longitudinal cohort study.

OBJECTIVE: To ascertain the microbiological consequences of WHO's recommendation for presumptive co-trimoxazole prophylaxis for infants with perinatal HIV exposure. METHODS: Using a longitudinal cohort design, we followed HIV-exposed and HIV-unexposed infants trimonthly for up to 18 months per infant. HIV-exposed infants received daily co-trimoxazole prophylaxis from 6 weeks to > or = 12 months of age. Using Streptococcus pneumoniae as our sentinel pathogen, we measured how co-trimoxazole altered nasopharyngeal colonization, pneumococcal resistance to antibiotics and serotype distribution as a function of co-trimoxazole exposure. FINDINGS: From 260 infants followed for 3096 patient-months, we detected pneumococci in 360/1394 (25.8%) samples. HIV-exposed infants were colonized more frequently than HIV-unexposed infants (risk ratio, RR: 1.4; 95% confidence interval, CI: 1.0-1.9, P = 0.04). Co-trimoxazole prophylaxis reduced colonization by ca 7% but increased the risk of colonization with co-trimoxazole-resistant pneumococci within 6 weeks of starting prophylaxis (RR: 3.2; 95% CI: 1.3-7.8, P = 0.04). Prophylaxis with co-trimoxazole led to a small but statistically significant increase of nasopharyngeal colonization with pneumococci not susceptible to clindamycin (RR: 1.6; 95% CI: 1.0-2.6, P = 0.04) but did not increase the risk of non-susceptibility to penicillin (RR: 1.1; 95% CI: 0.7-1.7), erythromycin (RR: 1.0; 95% CI: 0.6-1.7), tetracycline (RR: 0.9; 95% CI: 0.6-1.5) or chloramphenicol (RR: 0.8; 95% CI: 0.3-2.3). Co-trimoxazole prophylaxis did not cause the prevailing pneumococcal serotypes to differ from those that are targeted by the 7-valent conjugate pneumococcal vaccine (RR: 1.0; 95% CI: 0.7-1.6). CONCLUSION: Co-trimoxazole prophylaxis modestly suppresses pneumococcal colonization but accelerates infant acquisition of co-trimoxazole- and clindamycin-resistant pneumococci. Co-trimoxazole prophylaxis appears unlikely to compromise the future efficacy of conjugate vaccines.

Translation of artemether-lumefantrine treatment policy into paediatric clinical practice: an early experience from Kenya.

OBJECTIVE: To describe the quality of outpatient paediatric malaria case-management approximately 4-6 months after artemether-lumefantrine (AL) replaced sulfadoxine-pyrimethamine (SP) as the nationally recommended first-line therapy in Kenya. METHODS: Cross-sectional survey at all government facilities in four Kenyan districts. Main outcome measures were health facility and health worker readiness to implement AL policy; quality of antimalarial prescribing, counselling and drug dispensing in comparison with national guidelines; and factors influencing AL prescribing for treatment of uncomplicated malaria in under-fives. RESULTS: We evaluated 193 facilities, 227 health workers and 1533 sick-child consultations. Health facility and health worker readiness was variable: 89% of facilities stocked AL, 55% of health workers had access to guidelines, 46% received in-service training on AL and only 1% of facilities had AL wall charts. Of 940 children who needed AL treatment, AL was prescribed for 26%, amodiaquine for 39%, SP for 4%, various other antimalarials for 8% and 23% of children left the facility without any antimalarial prescribed. When AL was prescribed, 92% of children were prescribed correct weight-specific dose. AL dispensing and counselling tasks were variably performed. Higher health worker's cadre, in-service training including AL use, positive malaria test, main complaint of fever and high temperature were associated with better prescribing. CONCLUSIONS: Changes in clinical practices at the point of care might take longer than anticipated. Delivery of successful interventions and their scaling up to increase coverage are important during this process; however, this should be accompanied by rigorous research evaluations, corrective actions on existing interventions and testing cost-effectiveness of novel interventions capable of improving and maintaining health worker performance and health systems to deliver artemisinin-based combination therapy in Africa.

Effects of revised diagnostic recommendations on malaria treatment practices across age groups in Kenya.

OBJECTIVE: The recent change of treatment policy for uncomplicated malaria from sulfadoxine-pyrime-thamine to artemether-lumefantrine (AL) in Kenya was accompanied by revised malaria diagnosis recommendations promoting presumptive antimalarial treatment in young children and parasitological diagnosis in patients 5 years and older. We evaluated the impact of these age-specific recommendations on routine malaria treatment practices 4-6 months after AL treatment was implemented. METHODS: Cross-sectional, cluster sample survey using quality-of-care assessment methods in all government facilities in four Kenyan districts. Analysis was restricted to the 64 facilities with malaria diagnostics and AL available on the survey day. Main outcome measures were antimalarial treatment practices for febrile patients stratified by age, use of malaria diagnostic tests, and test result. RESULTS: Treatment practices for 706 febrile patients (401 young children and 305 patients > or =5 years) were evaluated. 43.0% of patients > or =5 years and 25.9% of children underwent parasitological malaria testing (87% by microscopy). AL was prescribed for 79.7% of patients > or =5 years with positive test results, for 9.7% with negative results and for 10.9% without a test. 84.6% of children with positive tests, 19.2% with negative tests, and 21.6% without tests were treated with AL. At least one antimalarial drug was prescribed for 75.0% of children and for 61.3% of patients > or =5 years with a negative test result. CONCLUSIONS: Despite different recommendations for patients below and above 5 years of age, malaria diagnosis and treatment practices were similar in the two age groups. Parasitological diagnosis was under-used in older children and adults, and young children were still tested. Use of AL was low overall and alternative antimalarials were commonly prescribed; but AL prescribing largely followed the results of malaria tests. Malaria diagnosis recommendations differing between age groups appear complex to implement; further strengthening of diagnosis and treatment practices under AL policy is required.

Control measures for malaria in pregnancy in India.

The purpose of this paper is to examine the current status of malaria in pregnancy (MiP) in India and review current control measures, programmes and interventions that work, and to suggest areas that need to be addressed. MiP can have serious health consequences for both the mother and infant, and thus presents a major public health challenge. Roll Back Malaria (RBM), a supporting agency of the World Health Organization (WHO), recommends reducing the burden of MiP through the following control measures: insecticide treated nets (ITNs), intermittent preventive therapy (IPTp), and effective case management. Even though India has a comprehensive national malaria programme, specific control measures aimed at decreasing the burden of MiP are limited in availability or are not adequately available. Components of the national malaria programme, which may serve to alleviate the MiP burden include the integration of malaria control with general health services and use of indoor residual spraying (IRS). These control strategies are beneficial because they reduce overall malaria exposure, both for pregnant women and the general population. However, there are several challenges and issues that India still faces regarding MiP. Major among them are the lack of ITNs, socio-cultural issues, growing resistance to antimalarials and insecticides, a new, yet to be fully implemented drug policy, and a highly centralized malaria control programme. A review of the current control measures for MiP in India indicates that these challenges and issues must be addressed in order to alleviate the MiP situation in India.