Rachel N. Musoke

Emergence of multidrug-resistant gram-negative organisms in a neonatal unit and the therapeutic implications

Multidrug-resistant organisms are increasing worldwide. Over the years we have noted increasing resistance of organisms isolated in our neonatal unit. There is a need therefore to scrutinize the problem so as to be able to plan for the future. Over a 5-month period, 716 infants were admitted of which 192 were screened for sepsis. Overall, 121 (16.7 per cent) had positive blood cultures. The predominant organisms were Gram negative (73.6 per cent of isolates) with Klebsiella species topping the list at 31 per cent. Case fatality for infants infected with Gram negative organisms was 41 per cent. Resistance to gentamicin was 20 per cent chloramphenicol 23.6 per cent, and amoxicillin/ampicillin 66.3 per cent. Of worry is the resistance to ceftazidime 19.1 per cent, and cefuroxime 21.3 per cent, with the figures rising to 27 per cent when more specialized tests are done (disc approximation and potentiation tests). If these drugs cannot be used in 20-27 per cent of cases then the situation is serious. The contributory factors to increased resistance include: non-investigation of infants put on antibiotics (50 per cent of cases); prolonged (73 per cent) and sometimes unjustified (41.7 per cent) use of antibiotics; and non-utilization of investigations when these are done (52 per cent) together with the delay in getting results back in the ward (6 days).

Factors affecting actualisation of the WHO breastfeeding recommendations in urban poor settings in Kenya.

Abstract Poor breastfeeding practices are widely documented in Kenya, where only a third of children are exclusively breastfed for 6 months and only 2% in urban poor settings. This study aimed to better understand the factors that contribute to poor breastfeeding practices in two urban slums in Nairobi, Kenya. In‐depth interviews (IDIs), focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with women of childbearing age, community health workers, village elders and community leaders and other knowledgeable people in the community. A total of 19 IDIs, 10 FGDs and 11 KIIs were conducted, and were recorded and transcribed verbatim. Data were coded in NVIVO and analysed thematically. We found that there was general awareness regarding optimal breastfeeding practices, but the knowledge was not translated into practice, leading to suboptimal breastfeeding practices. A number of social and structural barriers to optimal breastfeeding were identified: (1) poverty, livelihood and living arrangements; (2) early and single motherhood; (3) poor social and professional support; (4) poor knowledge, myths and misconceptions; (5) HIV; and (6) unintended pregnancies. The most salient of the factors emerged as livelihoods, whereby women have to resume work shortly after delivery and work for long hours, leaving them unable to breastfeed optimally. Women in urban poor settings face an extremely complex situation with regard to breastfeeding due to multiple challenges and risk behaviours often dictated to them by their circumstances. Macro‐level policies and interventions that consider the ecological setting are needed.

Viral Coinfections among African Children Infected with Human Immunodeficiency Virus Type 1

City-dwelling children from Kenya who were infected with human immunodeficiency virus type 1 (HIV-1) were tested for coinfection with cytomegalovirus (CMV), human T cell lymphotropic viruses 1 and 2, Kaposi sarcoma-associated herpesvirus (KSHV), or hepatitis B, C, and G viruses. All children were found to be coinfected with CMV, whereas 5% had hepatitis G virus coinfection and 15% had KSHV coinfection. A protective role for hepatitis G virus cannot be excluded but likely affects only a minority of HIV-1-infected African children.

Correlates of Delayed Disease Progression in HIV-1-Infected Kenyan Children

Without treatment most HIV-1-infected children in Africa die before their third birthday (>89%) and long-term nonprogressors are rare. The mechanisms underlying nonprogression in HIV-1-infected children are not well understood. In the present study, we examined potential correlates of delayed HIV disease progression in 51 HIV-1-infected African children. Children were assigned to progression subgroups based on clinical characterization. HIV-1-specific immune responses were studied using a combination of ELISPOT assays, tetramer staining, and FACS analysis to characterize the magnitude, specificity, and functional phenotype of HIV-1-specific CD8+ and CD4+ T cells. Host genetic factors were examined by genotyping with sequence-specific primers. HIV-1 nef gene sequences from infecting isolates from the children were examined for potential attenuating deletions. Thymic output was measured by T cell rearrangement excision circle assays. HIV-1-specific CD8+ T cell responses were detected in all progression groups. The most striking attribute of long-term survivor nonprogressors was the detection of HIV-1-specific CD4+ Th responses in this group at a magnitude substantially greater than previously observed in adult long-term nonprogressors. Although long-term survivor nonprogressors had a significantly higher percentage of CD45RA+CD4+ T cells, nonprogression was not associated with higher thymic output. No protective genotypes for known coreceptor polymorphisms or large sequence deletions in the nef gene associated with delayed disease progression were identified. In the absence of host genotypes and attenuating mutations in HIV-1 nef, long-term surviving children generated strong CD4+ T cell responses to HIV-1. As HIV-1-specific helper cells support anti-HIV-1 effector responses in active disease, their presence may be important in delaying disease progression.

Breastfeeding promotion: Feeding the low birth weight infant

Though there is still some reluctance to use human milk for low birth weight infants, we have shown that it is possible exclusively to feed these infants on milk from their own mothers. The infants have adequate weight gain and are less likely to get infections, especially gastrointestinal and respiratory. It is possible to sustain lactation through manual expression during the period that the mother is not nursing her infant directly on the breast. A cup rather than a bottle can be used to feed these small infants. The mothers are thus encouraged because the infant does not suffer nipple confusion with a bottle and they continue breastfeeding after discharge from the hospital.

Effectiveness of personalised, home-based nutritional counselling on infant feeding practices, morbidity and nutritional outcomes among infants in Nairobi slums: study protocol for a cluster randomised controlled trial

BackgroundNutrition in the first 1,000 days of life (during pregnancy and the first two years) is critical for child growth and survival. Poor maternal, infant and young child nutrition (MIYCN) practices are widely documented in Kenya, with potential detrimental effects on child growth and survival. This is particularly a problem in slums, where most urban residents live. For example, exclusive breastfeeding for the first six months is only about two per cent. Innovative strategies to reach slum residents are therefore needed. Strategies like the Baby Friendly Hospital Initiative have proven effective in some settings but their effectiveness in resource-limited settings, including slums where many women do not deliver in hospital, is questionable. We propose to test the effectiveness of a home-based intervention on infant feeding practices, nutrition and health outcomes of infants born in two slums in Nairobi, Kenya.Methods/DesignThe study, employing a cluster-randomised study design, will be conducted in two slums in Nairobi: Korogocho and Viwandani where 14 community units (defined by the Government’s health care system) will form the unit of randomization. A total of 780 pregnant women and their respective child will be recruited into the study. The mother-child pair will be followed up until the child is one year old. Recruitment will last approximately one year and three months from September 2012 to December 2013. The mothers will receive regular, personalised, home-based counselling by trained Community Health Workers on MIYCN. Regular assessment of knowledge, attitudes and practices on MIYCN will be done, coupled with assessments of nutritional status of the mother-child pairs and diarrhea morbidity for the children. Statistical methods will include analysis of covariance and multinomial logistic regression. Additionally, cost-effectiveness analysis will be done. The study is funded by the Wellcome Trust and will run from March 2012 to February 2015.DiscussionInterventions aimed at promoting optimal breastfeeding and complementary feeding practices are considered to have high impact and could prevent a fifth of the under-five deaths in countries with high mortality rates. This study will inform policy and practice in Kenya and similar settings regarding delivery mechanisms for such high-impact interventions, particularly among urban poor populations.Trial registrationISRCTN83692672

Postnatal weight gain of exclusively breast fed preterm African infants.

The weight of 64 preterm appropriate for gestational age infants were followed closely during the period of stay in the newborn unit. They were subdivided into three groups: A (1001-1250 g), B (1250-1500 g), and C (1501-1750 g). The mean gestation for these groups were 28.7, 30.5, and 31 weeks, respectively, while mean birth weights were 1132 +/- 81.7 g, 1377 +/- 85.6 g, and 1641 +/- 88.6 g. All were fed their own mothers breast milk during the period of study with no supplements. During the first week, there was significant weight loss in all groups as follows: A (12.0 per cent), B (7.7 per cent), and C (4.4 per cent). Thereafter, only group A lost weight in the second week, but the loss was not significant. Birth weights were regained at 23, 16, and 15 days, respectively. The weight gain after the initial loss was A (20.0 g), B (20.4 g), and C (20.2 g) per day. Group A had the fastest growth rate.

Rotavirus infections among HIV-infected children in Nairobi Kenya.

Human rotaviruses have emerged as a leading cause of acute diarrhea in children <5 years of age worldwide. Although there are previous reports relating to various aspects of rotaviruses, there is limited data on the involvement of rotavirus infection in HIV-infected children. We therefore evaluated the importance of rotavirus infections in HIV-related diarrhea in Kenyan children. Fecal samples were collected from a total of 207 children during the period February 1999 to June 2000 and screened for HRV antigen by enzyme-linked immunosorbent assay (ELISA). Positive samples were analyzed by VP6 subgroup specificity assay, by polyacrylamide gel electrophoresis (PAGE) and reverse transcriptase/polymerase chain reaction (RT-PCR). Fourteen percent (29/207) of the samples were positive. HIV-seropositive children with diarrhea were more likely than their counterparts without diarrhea to have rotaviruses [23.3% (10/43) versus 2.9% (2/70); p = 0.0001]. Rotavirus strain G3P[6] was predominant. These results indicate that rotavirus is an important viral etiological agent causing diarrhea in HIV-seropositive children.

Audit of care for children aged 6 to 59 months admitted with severe malnutrition at kenyatta national hospital, kenya.

We conducted a prospective audit of 101 children with severe malnutrition aged 6 to 59 months admitted to Kenyatta National Hospital, Kenyas largest tertiary level health facility, from February-April 2008. A structured tool was prepared to capture data to allow assessment of implementation of the WHO guidelines steps 1-8. Overall, 58% of children had marasmus and 47% of children were younger than one year old. Common co-morbidities at admission were diarrhoea (70.3%) and pneumonia (51.4%). The highest degree of implementation was observed for Step 5, treatment of potentially severe infections (90%, (95% CI 85.1-96.9)). Only 55% of the patients had F75 prescribed although this starter formula was available in this hospital. There was a delay in initiating feeds with a median time of 14.7 hours from the time of admission. There was modest implementation of Step 2, ensuring warmth (46.5%, 36.8-56.2), Step 3, treat dehydration (54.9%, 43.3-66.5) and Step 4, correct electrolyte imbalance, (45.5%, 35.6-55.8%). There was least implementation of Step 8, transition to catch-up feeding (23.8%, 13.6-34.0). We conclude that quality of care for children admitted with severe malnutrition at KNH is inadequate and often does not follow the WHO guidelines. Improving care will require a holistic and not simply medical approach.

Changes in the HIV Type 1 Envelope Gene from Non-Subtype B HIV Type 1-Infected Children in Kenya

A switch of coreceptor usage from CCR5 to CXCR4 occurs in about half of HIV-1-infected individuals in the natural course of infection. To investigate whether antiretroviral therapy (ART) enhances the coreceptor switch of HIV-1, we genotypically analyzed the env-V3 amino acid sequences from 81 HIV-1-infected children in Kenya whose plasma samples were obtained between 2000 and 2007. Of 41 children on ART, 35 had HIV-1 using CCR5 as a coreceptor at baseline. In 7 (20%) of them HIV-1 switched the coreceptor usage during the follow-up period. The mean duration of ART to the time of coreceptor switch was 2.6 years (range: 0.5-5.2). Of the remaining 40 children without ART, 32 had HIV-1 using CCR5 as a coreceptor at baseline and in 3 (9.4%) HIV-1 switched the coreceptor usage. The mean age of the children with HIV-1 coreceptor switch with and without ART was 7.3 and 9.7 years, respectively. The difference in the rate and age of coreceptor switch between treated and untreated children was not significant (p = 0.38 and 0.31, respectively). Of the HIV-1-infected children, 10 started ART by the age of 5 years (rapid progressors) and 23 did not need ART by the age of 10 years (slow progressors). The rate of coreceptor switch was strongly higher in rapid progressors (40%) than slow progressors (8.7%) (p = 0.053). These results suggest that switching of coreceptor usage from CCR5 to CXCR4 among HIV-1-infected children is not influenced by ART, but by factors responsible for rapid disease progression.