Benson Estambale

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

BACKGROUND Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. METHODS WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. FINDINGS Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5) and the NNT to achieve viral load suppression was 11 (5·8-227·3). INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings. FUNDING US Presidents Emergency Plan for AIDS Relief.

Spatial clustering of malaria and associated risk factors during an epidemic in a highland area of western Kenya

The epidemiology of malaria over small areas remains poorly understood, and this is particularly true for malaria during epidemics in highland areas of Africa, where transmission intensity is low and characterized by acute within and between year variations. We report an analysis of the spatial distribution of clinical malaria during an epidemic and investigate putative risk factors. Active case surveillance was undertaken in three schools in Nandi District, Western Kenya for 10 weeks during a malaria outbreak in May–July 2002. Household surveys of cases and age‐matched controls were conducted to collect information on household construction, exposure factors and socio‐economic status. Household geographical location and altitude were determined using a hand‐held geographical positioning system and landcover types were determined using high spatial resolution satellite sensor data. Among 129 cases identified during the surveillance, which were matched to 155 controls, we identified significant spatial clusters of malaria cases as determined using the spatial scan statistic. Conditional multiple logistic regression analysis showed that the risk of malaria was higher in children who were underweight, who lived at lower altitudes, and who lived in households where drugs were not kept at home.

Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial

Summary Background Malaria is a major cause of morbidity and mortality in early childhood, yet its consequences for health and education during the school-age years remain poorly understood. We examined the effect of intermittent preventive treatment (IPT) in reducing anaemia and improving classroom attention and educational achievement in semi-immune schoolchildren in an area of high perennial transmission. Methods A stratified, cluster-randomised, double-blind, placebo-controlled trial of IPT was done in 30 primary schools in western Kenya. Schools were randomly assigned to treatment (sulfadoxine-pyrimethamine in combination with amodiaquine or dual placebo) by use of a computer-generated list. Children aged 5–18 years received three treatments at 4-month intervals (IPT n=3535, placebo n=3223). The primary endpoint was the prevalence of anaemia, defined as a haemoglobin concentration below 110 g/L. This outcome was assessed through cross-sectional surveys 12 months post-intervention. Analysis was by both intention to treat, excluding children with missing data, and per protocol. This study is registered with ClinicalTrials.gov, number NCT00142246. Findings 2604 children in the IPT group and 2302 in the placebo group were included in the intention-to-treat analysis of the primary outcome; the main reason for exclusion was loss to follow-up. Prevalence of anaemia at 12 months averaged 6·3% in the IPT group and 12·6% in the placebo group (adjusted risk ratio 0·52, 95% CI 0·29–0·93; p=0·028). Significant improvements were also seen in two of the class-based tests of sustained attention, with a mean increase in code transmission test score of 6·05 (95% CI 2·83–9·27; p=0·0007) and counting sounds test score of 1·80 (0·19–3·41; p=0·03), compared with controls. No effect was shown for inattentive or hyperactive-compulsive behaviours or on educational achievement. The per-protocol analysis yielded similar results. 23 serious adverse events were reported within 28 days of any treatment (19 in the IPT group and four in the placebo group); the main side-effects were problems of balance, dizziness, feeling faint, nausea, and/or vomiting shortly after treatment. Interpretation IPT of malaria improves the health and cognitive ability of semi-immune schoolchildren. Effective malaria interventions could be a valuable addition to school health programmes. Funding Gates Malaria Partnership, the Norwegian Education Trust Fund and multidonor Education Development Programme Fund of the World Bank, DBL Centre for Health Research and Development, and the Wellcome Trust.

Earth-eating and reinfection with intestinal helminths among pregnant and lactating women in western Kenya

We conducted a longitudinal study among 827 pregnant women in Nyanza Province, western Kenya, to determine the effect of earth‐eating on geohelminth reinfection after treatment. The women were recruited at a gestational age of 14–24 weeks (median: 17) and followed up to 6 months postpartum. The median age was 23 (range: 14–47) years, the median parity 2 (range: 0–11). After deworming with mebendazole (500 mg, single dose) of those found infected at 32 weeks gestation, 700 women were uninfected with Ascaris lumbricoides, 670 with Trichuris trichiura and 479 with hookworm. At delivery, 11.2%, 4.6% and 3.8% of these women were reinfected with hookworm, T. trichiura and A. lumbricoides respectively. The reinfection rate for hookworm was 14.8%, for T. trichiura 6.65, and for A. lumbricoides 5.2% at 3 months postpartum, and 16.0, 5.9 and 9.4% at 6 months postpartum. There was a significant difference in hookworm intensity at delivery between geophagous and non‐geophagous women (P = 0.03). Women who ate termite mound earth were more often and more intensely infected with hookworm at delivery than those eating other types of earth (P = 0.07 and P = 0.02 respectively). There were significant differences in the prevalence of A. lumbricoides between geophagous and non‐geophagous women at 3 (P = 0.001) and at 6 months postpartum (P = 0.001). Women who ate termite mound earth had a higher prevalence of A. lumbricoides, compared with those eating other kinds of earth, at delivery (P = 0.02), 3 months postpartum (P = 0.001) and at 6 months postpartum (P = 0.001). The intensity of infections with T. trichiura at 6 months postpartum was significantly different between geophagous and non‐geophagous women (P = 0.005). Our study shows that geophagy is associated with A. lumbricoides reinfection among pregnant and lactating women and that intensities built up more rapidly among geophagous women. Geophagy might be associated with reinfection with hookworm and T. trichiura, although these results were less unequivocal. These findings call for increased emphasis, in antenatal care, on the potential risks of earth‐eating, and for deworming of women after delivery.

Prevention of anaemia in pregnancy using insecticide-treated bednets and sulfadoxine-pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial

To compare the effects of intermittent treatment with sulfadoxine-pyrimethamine (SP) given during the second and third trimester of pregnancy, the use of insecticide-treated nets (ITN), or the combination of both on haemoglobin (Hb) levels during pregnancy, a randomized, placebo-controlled intervention trial was conducted in a malaria-endemic area of western Kenya from July 1997 to September 1999. Primigravidae and secundigravidae were enrolled into the study and randomized into 4 intervention groups: (i) ITNs and SP, (ii) ITNs and placebo SP, (iii) SP alone, and (iv) placebo SP. All groups were offered case management and iron and folic acid supplementation. Seven hundred and fifty-two women were followed until delivery (53.2% were primigravidae and 46.8% secundigravidae). Among primigravidae in all the groups there was a significant improvement in Hb levels at delivery (107.6 g/L) compared with recruitment (101.9 g/L) (P < 0.006) with the greatest improvement in the combination ITNs + SP group. The protective efficacy of ITNs + SP on anaemia was 55.8% (95% CI 30.6-71.8), of SP alone 50.9% (95% CI 22.2-69.0), and of ITNs 41.6% (95% CI 9.8-62.3). Among secundigravidae, Hb levels were slightly lower at delivery compared with recruitment (P = 0.03). It was concluded that malaria is a major cause of anaemia in primigravidae but that other causes play a more significant role in secundigravidae, and that intermittent treatment with SP or use of ITNs benefits primigravidae more than secundigravidae.

Validity of the vaginal discharge algorithm among pregnant and non-pregnant women in Nairobi, Kenya.

Objective: To evaluate the validity of different algorithms for the diagnosis of gonococcal and chlamydial infections among pregnant and non-pregnant women consulting health services for vaginal discharge in Nairobi, Kenya. Methods: Cross sectional study among 621 women with complaints of vaginal discharge in three city council clinics between April and August 1997. Women were interviewed and examined for symptoms and signs of sexually transmitted infections (STIs). Specimens were obtained for laboratory diagnosis of genital infections, HIV, and syphilis. The data were used to evaluate the Kenyan flow chart as well as several other generated algorithms. Results: The mean age was 24 years and 334 (54%) were pregnant. The overall prevalence rates were: 50% candidiasis, 23% trichomoniasis, 9% bacterial vaginosis, 7% gonorrhoea, 9% chlamydia, 7% syphilis, and 22% HIV. In non-pregnant women, gonococcal and chlamydial infection was significantly associated with (1) demographic and behavioural risk markers such as being single, younger than 20 years, multiple sex partners in the previous 3 months; (2) symptom fever; and (3) signs including presence of yellow or bloody vaginal discharge, cervical mucopus, cervical erythema, and friability. Among pregnant women only young age, dysuria, and fever were significantly associated with cervical infection. However, none of these variables was either sensitive or specific enough for the diagnosis of cervical infection. Several algorithms were generated and applied to the study data. The algorithm including risk markers performed slightly better than the current Kenyan algorithm. Conclusion: STIs form a major problem in the Nairobi area and should be addressed accordingly. None of the tested algorithms for the treatment of vaginal discharge would constitute a marked improvement of the existing flow chart. Hence, better detection tools for the specific aetiology of vaginal discharge are urgently needed.

Relationships between anaemia and parasitic infections in Kenyan schoolchildren: A Bayesian hierarchical modelling approach

Anaemia is multi-factorial in origin and disentangling its aetiology remains problematic, with surprisingly few studies investigating the relative contribution of different parasitic infections to anaemia amongst schoolchildren. We report cross-sectional data on haemoglobin, malaria parasitaemia, helminth infection and undernutrition among 1523 schoolchildren enrolled in classes 5 and 6 (aged 10–21 years) in 30 primary schools in western Kenya. Bayesian hierarchical modelling was used to investigate putative relationships. Children infected with Plasmodium falciparum or with a heavy Schistosoma mansoni infection, stunted children and girls were found to have lower haemoglobin concentrations. Children heavily infected with S. mansoni were also more likely to be anaemic compared with uninfected children. This study further highlights the importance of malaria and intestinal schistosomiasis as contributors to reduced haemoglobin levels among schoolchildren and helps guide the implementation of integrated school health programmes in areas of differing parasite transmission.

Human papillomavirus types in women with invasive cervical carcinoma by HIV status in Kenya

To evaluate the fraction of invasive cervical carcinoma (ICC) that could be prevented in HIV‐infected women by vaccines currently available against human papillomavirus (HPV)16 and 18, we conducted a cross‐sectional study in women with ICC in Nairobi, Kenya. Fifty‐one HIV‐positive women were frequency‐matched by age to 153 HIV‐negative women. Cervical cells were tested for HPV DNA using polymerase chain reaction‐based assays (SPF10‐INNO‐LiPA). Comparisons were adjusted for multiplicity of HPV types. As expected, multiple‐type infections were much more frequent in HIV‐positive (37.2%) than in HIV‐negative (13.7%) women, but the distribution of HPV types was similar. HPV16 was detected in 41.2% versus 43.8% and HPV16 and/or 18 in 64.7% versus 60.1% of HIV‐positive versus HIV‐negative women, respectively. The only differences of borderline statistical significance were an excess of HPV52 (19.6% versus 5.2%) and a lack of HPV45 (7.8% versus 17.0%) in HIV‐positive women compared to HIV‐negative women, respectively. We have been able to assess an unprecedented number of ICCs in HIV‐positive women, but as we did not know the age of HIV acquisition, we cannot exclude that it had occurred too late in life to affect the type of HPV involved in cervical carcinogenesis. However, if our findings were confirmed, they would suggest that the efficacy of current vaccines against HPV16 and 18 to prevent ICC is similar in HIV‐positive and HIV‐negative women, provided vaccination is administered before sexual debut, as recommended.

Prevalence of human papillomavirus in women with invasive cervical carcinoma by HIV status in Kenya and South Africa.

Data on the prevalence of human papillomavirus (HPV) types in cervical carcinoma in women with HIV are scarce but are essential to elucidate the influence of immunity on the carcinogenicity of different HPV types, and the potential impact of prophylactic HPV vaccines in populations with high HIV prevalence. We conducted a multicentre case–case study in Kenya and South Africa. During 2007–2009, frozen tissue biopsies from women with cervical carcinoma were tested for HPV DNA using GP5+/6+‐PCR assay. One hundred and six HIV‐positive (mean age 40.8 years) and 129 HIV‐negative women (mean age 45.7) with squamous cell carcinoma were included. Among HIV‐positive women, the mean CD4 count was 334 cells/μL and 48.1% were on combined antiretroviral therapy. HIV‐positive women had many more multiple HPV infections (21.6% of HPV‐positive carcinomas) compared with HIV‐negative women (3.3%) (p < 0.001) and the proportion of multiple infections was inversely related to CD4 level. An excess of HPV18 of borderline statistical significance was found in HIV‐positive compared with HIV‐negative cases (Prevalence ratio (PR) = 1.9, 95% confidence interval (CI): 1.0–3.7, adjusted for study centre, age and multiplicity of infection). HPV16 and/or 18 prevalence combined, however, was similar in HIV‐positive (66.7%) and HIV‐negative cases (69.1%) (PR = 1.0, 95% CI: 0.9–1.2). No significant difference was found for other HPV types. Our data suggest that current prophylactic HPV vaccines against HPV16 and 18 may prevent similar proportions of cervical SCC in HIV‐positive as in HIV‐negative women provided that vaccine‐related protection is sustained after HIV infection.

HIV and cervical cancer in Kenya

Objectives: To determine the effect of the HIV epidemic on invasive cervical cancer in Kenya. Methods: Of the 3902 women who were diagnosed with reproductive tract malignancies at Kenyatta National Hospital (KNH) from 1989 to 1998, 85% had invasive cervical cancer. Age at presentation and severity of cervical cancer were studied for a 9‐year period when national HIV prevalence went from 5% to 5–10%, to 10–15%. Results: There was no significant change in either age at presentation or severity of cervical cancer. Of the 118 (5%) women who were tested for HIV, 36 (31%) were seropositive. These women were 5 years younger at presentation than HIV‐negative women. Conclusions: A two‐ to three‐fold increase in HIV prevalence in Kenya did not seem to have a proportional effect on the incidence of cervical cancer. Yet, HIV‐positive women who presented with cervical cancer were significantly younger than HIV‐negative women.