Rapid situational assessment of people who inject drugs (PWID) in Nairobi and coastal regions of Kenya: a respondent driven sampling survey.

BACKGROUND: A Cross-sectional Rapid Situational Assessment of People Who Inject Drug (PWIDs) applying Respondent Driven sampling techniques (RDS) was used to recruit subjects/participants in a study aimed at assessing HIV prevalence and risk behaviors among injecting drug users in Nairobi and Coastal regions of Kenya. There is paucity of data and information on injecting drug use in sub-Saharan Africa and there is sufficient evidence of existence of the environment for development and growth of injecting drug use. Past studies on PWID and its association to HIV and AIDS that have been conducted in Kenya do not provide sufficient information to support effective planning and comprehensive national response to the HIV and AIDS epidemic. METHODS: A cross-sectional study design was adopted in which a set of initial subjects referred to as 'seeds' were first identified from which an expanding chain of referrals were obtained, with subjects from each wave referring subjects of subsequent waves. The seeds were drawn randomly from the population and interviewed to pick the one with the largest network and other unique characteristics. A maximum of twelve seeds were recruited. The second stage involved conducting assessment visits to the sites to identify potential collaborators that included non-governmental organizations (NGOs), drug treatment centres, health facilities, community based organizations (CBO's) among others. Three NGOs located in the coast region and one in Nairobi region were identified to assist in identifying drug injection locations and potential participants. Key informant interviews (KIIs) and Focus Group Discussions (FGDs) were also conducted using interview guides. RESULTS: A total of 646 individuals (344 in Nairobi and 302 at the coast) were recruited for the study between January and March 2010. Of these 590 (91%) were male and 56 (9%) were female. Findings showed that most PWIDs initiated injecting drug use between the ages of 20-29 years, with the youngest age of initiation being 11 years and oldest age being 53 years. Most commonly injected drug was heroin (98%), with a small (2%) percentage injecting cocaine. Other non-injecting methods such as smoking or combining these two drugs with other drugs such as cannabis or Rohypnol were also common. Most PWIDs used other substances (cigarettes, alcohol, and cannabis) before initiating injecting drug use. The adjusted national HIV prevalence of PWIDs was 18.3% (19.62% unadjusted) with PWIDs in Nairobi region registering 18.33% (20.58% unadjusted) compared PWIDs for Coastal region indicating 18.27% (18.59% - unadjusted). The gender based HIV prevalence showed that women were more at risk of acquiring HIV (44.51%-adjusted) compared to men (15.97%-adjusted). The age specific HIV prevalence showed that PWIDs who initiated injecting at 11-19 years (44.7% adjusted) were most at risk in Nairobi compared to those who initiated injecting at age 20-24 years (23.2% - adjusted) in the coastal region. While all PWIDs continue to be at risk in the two regions, those from the Western parts of Nairobi, Kenya were at a relatively higher risk given their increased propensity for sharing injecting equipment and solutions. CONCLUSIONS: Compared to the national HIV prevalence of (4.9%), the results show that People Who Inject Drugs (PWIDs) are at particularly high risk of infection in Kenya and there is urgent need for intervention (KenPHIA, 2018). This study also showed clear evidence that 70% of PWIDs are primary school educated, engage in high risk injecting and sexual behaviors comprising sharing of injecting equipment, unprotected heterosexual and homosexual sex. Given that initiation of injecting drug use begins early and peaks after formal school years (20-29 years), prevention programmes should be targeted at primary and secondary school students, college and out of school youth. Further, to protect People who inject drugs (PWIDs) from HIV infection, the country should introduce free Needle Syringe Programs (NSP) with provision of condoms and Methadone Assisted Therapy (MAT) as a substitute for drug use.

Erratum: Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains.

[This corrects the article DOI: 10.1093/ve/vey027.][This corrects the article DOI: 10.1093/ve/vey027.].

Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains.

The respiratory syncytial virus (RSV) group A variant with the 72-nucleotide duplication in the G gene, genotype ON1, was first detected in Kilifi in 2012 and has almost completely replaced circulating genotype GA2 strains. This replacement suggests some fitness advantage of ON1 over the GA2 viruses in Kilifi, and might be accompanied by important genomic substitutions in ON1 viruses. Close observation of such a new virus genotype introduction over time provides an opportunity to better understand the transmission and evolutionary dynamics of the pathogen. We have generated and analysed 184 RSV-A whole-genome sequences (WGSs) from Kilifi (Kenya) collected between 2011 and 2016, the first ON1 genomes from Africa and the largest collection globally from a single location. Phylogenetic analysis indicates that RSV-A circulation in this coastal Kenya location is characterized by multiple introductions of viral lineages from diverse origins but with varied success in local transmission. We identified signature amino acid substitutions between ON1 and GA2 viruses' surface proteins (G and F), polymerase (L), and matrix M2-1 proteins, some of which were positively selected, and thereby provide an enhanced picture of RSV-A diversity. Furthermore, five of the eleven RSV open reading frames (ORFs) (G, F, L, N, and P) formed distinct phylogenetic clusters for the two genotypes. This might suggest that coding regions outside of the most frequently studied G ORF also play a role in the adaptation of RSV to host populations, with the alternative possibility that some of the substitutions are neutral and provide no selective advantage. Our analysis provides insight into the epidemiological processes that define RSV spread, highlights the genetic substitutions that characterize emerging strains, and demonstrates the utility of large-scale WGS in molecular epidemiological studies.

Refining a questionnaire to assess breast cancer knowledge and barriers to screening in Kenya: Psychometric assessment of the BCAM.

BACKGROUND: Our study objective was to determine the validity and reliability of the breast module of a cancer awareness measure (BCAM) among adult women in western Kenya. METHODS: The study was conducted between October and November 2012, following three breast cancer screening events. Purposive and systematic random sampling methods were used to identity 48 women for cognitive focus group discussions, and 1061 (594 who attended vs. 467 who did not attend screening events) for surveys, respectively. Face and psychometric validity of the BCAM survey was assessed using cognitive testing, factor analysis of survey data, and correlations. Internal reliability was assessed using Cronbach's alpha. RESULTS: Among survey participants, the overall median age was 34 (IQR: 26-44) years. Compared to those women who did not attend the screening events, women attendees were older (median: 35 vs. 32 years, p = 0.001) more often married (79% vs. 72%, p = 0.006), more educated (52% vs. 46% with more than an elementary level of education, p = 0.001), more unemployed (59% vs. 11%, p = 0.001), more likely to report doing breast self-examination (56% vs. 40%, p = 0.001) and more likely to report having felt a breast lump (16% vs. 7%, p = 0.001). For domain 1 on knowledge of breast cancer symptoms, one factor (three items) with Eigen value of 1.76 emerged for the group that did not attend screening, and 1.50 for the group that attended screening. For both groups two factors (factor 1 "internal influences" and factor 2 "external influences") emerged among domain 4 on barriers to screening, with varied item loadings and Eigen values. There were no statistically significant differences in the factor scores between attendees and non-attendees. There were significant associations between factor scores and other attributes of the surveyed population, including associations with occupation, transportation type, and training for and practice of breast self-examination. Cronbach's alpha showed an acceptable internal consistency. CONCLUSION: Certain subpopulations are less likely than others to attend breast screening in Kenya. A survey measure of breast cancer knowledge and perceived barriers to screening shows promise for use in Kenya for characterizing clinical and community population beliefs, but needs adaptation for setting, language and culture.

Impact of an educational intervention on breast cancer knowledge in western Kenya.

Our objective was to assess the effectiveness of educational sessions that accompanied breast cancer screening events in three communities in western Kenya between October and November 2013. Five hundred and thirty-two women were recruited to complete a test of breast cancer-relevant knowledge and randomly allocated to 'pre-test' or 'post-test' groups that immediately preceded or followed participation in the educational sessions. The education was organized as a presentation by health professionals and focused mainly on causes of breast cancer, early and late cancer presentation signs, high-risk groups, screening methods to find early-stage breast cancer, self-breast exam procedures and treatment options for this disease. Participants were invited to ask questions and practice finding nodules in silicone breast models. The median age was 35 years (interquartile range: 28-45), and 86% had not undergone breast cancer screening previously. Many individual items in our test of knowledge showed statistically significant shifts to better-informed responses. When all items in the assessment questionnaire were scored as a 'test', on average there was a 2.80 point (95% CI: 2.38, 3.22) significant improvement in knowledge about breast cancer after the educational session. Our study provides evidence for the effectiveness of an educational strategy carefully tailored for women in these communities in Kenya.

Early biting of the Anopheles gambiae s.s. and its challenges to vector control using insecticide treated nets in western Kenya highlands.

Long term use of insecticides in malaria vector control has been shown to alter the behavior of vectors. Such behavioral shifts have the potential of undermining the effectiveness of insecticide-based control interventions. The effects of insecticide treated nets (ITNs) use on the composition, biting/feeding and sporozoite rates of Anopheles gambiae s.l. mosquitoes in Musilongo village, Vihiga County of western Kenya highlands were investigated. Adult mosquitoes were collected in selected sleeping spaces inside six randomly selected houses using miniature Centre for Disease Control and Prevention (CDC) light traps. Mosquito sampling in each house was conducted twice every week for 16 consecutive months (May 2010-August 2012). At each sampling a single trap was set in the selected space inside each house such that it collected mosquitoes alternatively from 18:00 to 21:00h and 21:00 to 06:00h every week. All collected mosquitoes were morphologically identified. Female Anopheles mosquitoes were classified according to their physiological status as unfed, fed, partially gravid and gravid, sorted and counted. Members of the A. gambiae complex were identified using a Polymerase chain reaction (PCR) method. Enzyme-linked-immunosorbent assay (ELISA) was used to determine blood meal sources and Plasmodium infection rates in A. gambiae s.l. mosquitoes. Blood meal tests were conducted on DNA extracted from gut contents of blood fed A. gambiae s.l. The head and thorax section of dried samples of A. gambiae s.l. were used in testing for the presence of Plasmodium falciparum (Pf) sporozoites. Overall, 735 adult female Anopheles comprising 708 [96.3%] A. gambiae s.l. and 27 [3.7%] Anopheles funestus mosquitoes were collected. A. gambiae s.l. population collected comprised, 615 [86.9%] unfed and 38 [5.4%] fed adult mosquitoes. The rest were either partially or fully gravid. The proportion of A. gambiae s.l. biting indoors within 18:00-21:00h was 15.8% (103/653) at a rate of 3.2bites per person per hour compared to 84.2% biting from 21:00-06:00h at a rate of 3.8 bites/per/h. An estimated 97.7% A. gambiae ss and 2.3% A. arabiensis constituted the indoor biting A. gambiae s.l. The population of An. gambiae s.l. biting from 18:00 to 21:00h had a Plasmodium faciparum (pf) sporozoite rate of 3.8% compared to 3.5% observed in populations biting within 21:00-06:00h. Human blood constituted 89% of An. gambiae s.l. blood meal sources. The risk of malaria transmission from 21:00 to 06:00h was approximately 5 fold the risk within 18:00-21:00h. Majority of the infective female A. gambiae s.l. adults were biting deep into the night than in the early hours of the night. Humans remain the preferred source of blood meal for A. gambiae s.s. the dominant malaria vector in the highlands. ITNs remain a fundamental control intervention against malaria transmission since female blood seekers were more during bed time than pre-bed time. Advocacy on enhanced net availability, integrity and usage in Kenyan highlands can reduce Pf transmission. Additional complementary interventions are required to control the biting and parasite transmission encountered before bed-time.

Prevalence, incidence and risk factors of epilepsy in older children in rural Kenya.

BACKGROUND: There is little data on the burden or causes of epilepsy in developing countries, particularly in children living in sub-Saharan Africa. METHODS: We conducted two surveys to estimate the prevalence, incidence and risk factors of epilepsy in children in a rural district of Kenya. All children born between 1991 and 1995 were screened with a questionnaire in 2001 and 2003, and those with a positive response were then assessed for epilepsy by a clinician. Active epilepsy was defined as two or more unprovoked seizures with one in the last year. RESULTS: In the first survey 10,218 children were identified from a census, of whom 110 had epilepsy. The adjusted prevalence estimates of lifetime and active epilepsy were 41/1000 (95% CI: 31-51) and 11/1000 (95% CI: 5-15), respectively. Overall two-thirds of children had either generalized tonic-clonic and/or secondary generalized seizures. A positive history of febrile seizures (OR=3.01; 95% CI: 1.50-6.01) and family history of epilepsy (OR=2.55; 95% CI: 1.19-5.46) were important risk factors for active epilepsy. After the second survey, 39 children from the same birth cohort with previously undiagnosed epilepsy were identified, thus the incidence rate of active epilepsy is 187 per 100,000 per year (95% CI: 133-256) in children aged 6-12 years. CONCLUSIONS: There is a considerable burden of epilepsy in older children living in this area of rural Kenya, with a family history of seizures and a history of febrile seizures identified as risk factors for developing epilepsy.

Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.

OBJECTIVE: Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine. DESIGN: This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator. SETTING: The study was conducted in a rural population in Kombewa Division, western Kenya. PARTICIPANTS: Subjects were 135 children, aged 12-47 mo. INTERVENTIONS: Subjects received 10, 25, or 50 microg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 microL, respectively, of AS02A, or they received a comparator (Imovax (rabies vaccine). OUTCOME MEASURES: We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination. RESULTS: Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 microg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 microg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F(3,1047) = 10.78, or F(3, 995) = 11.22, p < 0.001); however, the comparison of 25 microg and 50 microg recipients indicated no significant difference (F(1,1047) = 0.05; p = 0.82). CONCLUSIONS: The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.

Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions.

AIMS: Convulsions are a common complication of severe malaria in children and are associated with poor outcome. Diazepam is used to terminate convulsions but its pharmacokinetics and pharmacodynamics have not been studied in this group. Accordingly, we carried out a comparative study of the pharmacokinetics of intravenous (i.v.) and rectal (p.r.) diazepam. METHODS: Twenty-five children with severe malaria and a convulsion lasting >5 min were studied. Sixteen children received diazepam intravenously (i.v.; 0.3 mg kg(-1)) and nine rectally (p.r.; 0.5 mg kg(-1)). Plasma diazepam concentrations were measured by reversed phase high-performance liquid chromatography. The duration of convulsions, depth of coma, respiratory and cardiovascular parameters were monitored. RESULTS: Median maximum plasma diazepam concentrations of 634 (range 402-1507) ng ml(-1) and 423 (range 112-1953) ng ml(-1) were achieved at 5 and 25 min following i.v. and p.r. administration, respectively. All patients except three (one i.v. and two p.r.) achieved plasma diazepam concentration >200 ng ml(-1) within 5 min. Following p.r. administration, plasma diazepam concentrations were more variable than i.v. administration. A single dose of i.v. diazepam terminated convulsions in all children but in only 6/9 after p.r. administration. However, nine children treated with i.v. and all those treated with p.r. diazepam had a recurrence of convulsions occurring at median plasma diazepam concentrations of 157 (range: 67-169) and 172 (range: 74-393) ng ml(-1) , respectively. All the children in the i.v. and four in the PR diazepam group who had recurrence of convulsions required treatment. None of the children developed respiratory depression or hypotension. CONCLUSIONS: Administration of diazepam i.v. or p.r. resulted in achievement of therapeutic concentrations of diazepam rapidly, without significant cardio-respiratory adverse effects. However, following p.r. administration, diazepam did not terminate all convulsions and plasma drug concentrations were more variable.

Changing home treatment of childhood fevers by training shop keepers in rural Kenya.

BACKGROUND: Malaria control in Africa relies primarily on early effective treatment for clinical disease, but most early treatments for fever occur through self-medication with shop-bought drugs. Lack of information to community members on over-the-counter drug use has led to widespread ineffective treatment of fevers, increased risks of drug toxicity and accelerating drug resistance. We examined the feasibility and measured the likely impact of training shop keepers in rural Africa on community drug use. METHODS: In a rural area of coastal Kenya, we implemented a shop keeper training programme in 23 shops serving a population of approximately 3500, based on formative research within the community. We evaluated the training by measuring changes in the proportions of drug sales where an adequate amount of chloroquine was purchased and in the percentage of home-treated childhood fevers given an adequate amount of chloroquine. The programme was assessed qualitatively in the community following the shop keeper training. RESULTS: The percentage of drug sales for children with fever which included an antimalarial drug rose from 34.3% (95% CI 28.9%-40.1%) before the training to a minimum of 79.3% (95% CI 71.8%-85.3%) after the training. The percentage of antimalarial drug sales where an adequate amount of drug was purchased rose from 31.8% (95% CI 26.6%-37.6%) to a minimum of 82.9% (95% CI 76.3%-87.3%). The percentage of childhood fevers where an adequate dose of chloroquine was given to the child rose from 3.7% (95% CI 1.2%-9.7%) before the training to a minimum of 65.2% (95% CI 57.7%-72.0%) afterwards, which represents an increase in the appropriate use of over-the-counter chloroquine by at least 62% (95% CI 53.7%-69.3%). Shop keepers and community members were strongly supportive of the aims and outcome of the programme. CONCLUSIONS: The large shifts in behaviour observed indicate that the approach of training shop keepers as a channel for information to the community is both feasible and likely to have a significant impact. Whilst some of the impact seen may be attributable to research effects in a relatively small scale pilot study, the magnitude of the changes support further investigation into this approach as a potentially important new strategy in malaria control.

Markers in HIV associated tuberculosis in Kenya.

Tuberculosis is one of the most frequent opportunistic infections in HIV-infected patients in developing countries. In some instances, manifestations of pulmonary tuberculosis precede all other HIV related signs and symptoms because of the high virulence of M. tuberculosis. In order to characterise the interaction between these two pathogens, clinical and immunological parameters in pulmonary tuberculosis patients with and without HIV infection were compared. Amongst newly diagnosed pulmonary tuberculosis patients the association of some of these changes with the clinical outcome were evaluated. Of these, 44% were co-infected with HIV. Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone, P= 0.0292. Low CD4+ lymphocyte counts, lymphadenopathy and BCG scar absence could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients.

Clinical and immunological markers in Kenyan pulmonary tuberculosis patients with and without HIV-1.

Amongst newly diagnosed pulmonary tuberculosis patients, 44% were co-infected with human immunodeficiency virus (HIV). Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone, P = 0.0292. CD4+ lymphocyte counts, lymphadenopathy and BCG scar could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients.

PIP: 87 newly diagnosed pulmonary tuberculosis (PTB) patients at the Infectious Diseases Hospital, Nairobi, Kenya, were recruited into the study. Only patients with acid fast bacilli on stained smears of expectorated sputum were considered to have PTB. Cases were presumed PTB when a negative sputum smear was obtained in a patient with clinical and radiographic features consistent with PTB. Heparinized peripheral venous blood from each patient was tested for antibodies to HIV-1 with the Dupont HTLV 111 and the Wellcozyme Diagnostics ELISA. Only samples seropositive with both ELISAs were considered HIV-1 seropositive. T-lymphocyte subpopulation was separated from mononuclear cells by centrifugation on a Ficoll-Hypaque gradient. There were approximately equal numbers of males and females (25 males and 24 females) in the HIV-1 negative group but as many as 26 males compared to 12 females in the HIV-1 positive group. The sex ratio in the HIV-1 negative was M/F; 1:0.96 and M/F; 1:0.5 in the HIV-1 positive group. The mean age of patients with HIV-1 (33.4 +or- 7.22) was significantly higher than those without HIV-1 (28.70 +or- 11.20; p0.001). The overall prevalence of HIV-1 was 44%; higher in men (30%) than in women (14%). The hemoglobin (12.0 +or- 2.6 gm HIV-1 negative; 12.0 +or- 1.4.0 gm HIV-1 positive) and total lymphocyte counts (2451.6 +or- 1036.7/cubic mm HIV-1 negative; 2020.9 +or- 1258.6/cubic mm HIV-1 positive) were not significantly different between the 2 groups. However, the white blood cell count was significantly higher in HIV-1 seronegative group (7273.5 +or- 4700/cubic mm) than in the HIV-1 seropositive group (5094.8 +or- 3494/cubic mm); p0.05). Patients with HIV-1 presented more often with lymphadenopathy, diarrhea and weight loss, whereas cough and fever were as common in HIV-1 positive as HIV-1 negative patients. Even though CD3, CD4, and CD8 counts were significantly lower in HIV-1 positive patients, the ratio of CD4/CD8 was not significantly different between the 2 groups.

Markers in HIV Associated Tuberculosis in Kenya

Tuberculosis is one of the most frequent opportunistic infections in HIV-infected patients in developing countries. In some instances; manifestations of pulmonary tuberculosis precede all other HIV related signs and symptoms because of the high virulence of M. tuberculosis. In order to characterise the interaction between these two pathogens; clinical and immunological parameters in pulmonary tuberculosis patients with and without HIV infection were compared. Amongst newly diagnosed pulmonary tuberculosis patients the association of some of these changes with the clinical outcome were evaluated. Of these; 44were co-infected with HIV. Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone; P= 0.0292. Low CD4+ lymphocyte counts; lymphadenopathy and BCG scar absence could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients