Abraham Katana

Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial.

BACKGROUNDnEvery year, more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences. The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance. We aimed to assess the efficacy and safety of two alternative strategies: intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine, and intermittent preventive treatment with dihydroartemisinin-piperaquine.nnnMETHODSnWe did this open-label, three-group, randomised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-negative pregnant women between 16 and 32 weeks gestation were randomly assigned (1:1:1), via computer-generated permuted-block randomisation (block sizes of three, six, and nine), to receive intermittent screening and treatment with dihydroartemisinin-piperaquine, intermittent preventive treatment with dihydroartemisinin-piperaquine, or intermittent preventive treatment with sulfadoxine-pyrimethamine. Study participants, study clinic nurses, and the study coordinator were aware of treatment allocation, but allocation was concealed from study investigators, delivery unit nurses, and laboratory staff. The primary outcome was malaria infection at delivery, defined as a composite of peripheral or placental parasitaemia detected by placental histology, microscopy, or rapid diagnostic test. The primary analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01669941.nnnFINDINGSnBetween Aug 21, 2012, and June 19, 2014, we randomly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine (n=515), intermittent preventive treatment with dihydroartemisinin-piperaquine (n=516), or intermittent preventive treatment with sulfadoxine-pyrimethamine (n=515); 1368 (88%) women comprised the intention-to-treat population for the primary endpoint. Prevalence of malaria infection at delivery was lower in the intermittent preventive treatment with dihydroartemisinin-piperaquine group than in the intermittent preventive treatment with sulfadoxine-pyrimethamine group (15 [3%] of 457 women vs 47 [10%] of 459 women; relative risk 0·32, 95% CI 0·18-0·56; p<0·0001), but not in the intermittent screening and treatment with dihydroartemisinin-piperaquine group (57 [13%] of 452 women; 1·23, 0·86-1·77; p=0·26). Compared with intermittent preventive treatment with sulfadoxine-pyrimethamine, intermittent preventive treatment with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria infection during pregnancy (192·0 vs 54·4 events per 100 person-years; incidence rate ratio [IRR] 0·28, 95% CI 0·22-0·36; p<0·0001) and clinical malaria during pregnancy (37·9 vs 6·1 events; 0·16, 0·08-0·33; p<0·0001), whereas intermittent screening and treatment with dihydroartemisinin-piperaquine was associated with a higher incidence of malaria infection (232·0 events; 1·21, 1·03-1·41; p=0·0177) and clinical malaria (53·4 events; 1·41, 1·00-1·98; p=0·0475). We recorded 303 maternal and infant serious adverse events, which were least frequent in the intermittent preventive treatment with dihydroartemisinin-piperaquine group.nnnINTERPRETATIONnAt current levels of rapid diagnostic test sensitivity, intermittent screening and treatment is not a suitable alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine in the context of high sulfadoxine-pyrimethamine resistance and malaria transmission. However, dihydroartemisinin-piperaquine is a promising alternative drug to replace sulfadoxine-pyrimethamine for intermittent preventive treatment. Future studies should investigate the efficacy, safety, operational feasibility, and cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine.nnnFUNDINGnThe Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine.

An Analysis of Pregnancy-Related Mortality in the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya

Background Pregnancy-related (PR) deaths are often a result of direct obstetric complications occurring at childbirth. Methods and Findings To estimate the burden of and characterize risk factors for PR mortality, we evaluated deaths that occurred between 2003 and 2008 among women of childbearing age (15 to 49 years) using Health and Demographic Surveillance System data in rural western Kenya. WHO ICD definition of PR mortality was used: “the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death”. In addition, symptoms and events at the time of death were examined using the WHO verbal autopsy methodology. Deaths were categorized as either (i) directly PR: main cause of death was ascribed as obstetric, or (ii) indirectly PR: main cause of death was non-obstetric. Of 3,223 deaths in women 15 to 49 years, 249 (7.7%) were PR. One-third (34%) of these were due to direct obstetric causes, predominantly postpartum hemorrhage, abortion complications and puerperal sepsis. Two-thirds were indirect; three-quarters were attributable to human immunodeficiency virus (HIV/AIDS), malaria and tuberculosis. Significantly more women who died in lower socio-economic groups sought care from traditional birth attendants (pu200a=u200a0.034), while less impoverished women were more likely to seek hospital care (pu200a=u200a0.001). The PR mortality ratio over the six years was 740 (95% CI 651–838) per 100,000 live births, with no evidence of reduction over time (χ2 linear trendu200a=u200a1.07; pu200a=u200a0.3). Conclusions These data supplement current scanty information on the relationship between infectious diseases and poor maternal outcomes in Africa. They indicate low uptake of maternal health interventions in women dying during pregnancy and postpartum, suggesting improved access to and increased uptake of skilled obstetric care, as well as preventive measures against HIV/AIDS, malaria and tuberculosis among all women of childbearing age may help to reduce pregnancy-related mortality.

Mother-to-child transmission of HIV in Kenya: results from a nationally representative study.

Background:Kenya has an estimated 13,000 new infant HIV infections that occur annually. We measured the burden of HIV infection among women of childbearing age and assessed access to and coverage of key prevention of mother-to-child transmission interventions. Methods:The second Kenya AIDS Indicator Survey was a nationally representative 2-stage cluster sample of households. We analyzed data from women aged 15–54 years who had delivered a newborn within the preceding 5 years and from whom we obtained samples for HIV testing. Results:Of 3310 women who had ≥1 live birth in the preceding 5 years, 2862 (86.5%) consented to HIV testing in the survey, and 171 (6.1%) were found to be infected. Ninety-five percent received prenatal care, 93.1% were screened for HIV during prenatal care, and of those screened, 97.8% received their test results. Seventy-six women were known to be infected in their last pregnancy. Of these, 54 (72.3%) received antepartum antiretroviral prophylaxis, and 51 (69.1%) received intrapartum prophylaxis; 56 (75.3%) reported their newborns received postpartum prophylaxis. Of the 76 children born to these mothers, 63 (82.5%) were tested for HIV at the first immunization visit or thereafter, and 8 (15.1%) were HIV infected. Conclusions:We found a substantial burden of HIV in Kenyan women of childbearing age and a cumulative 5-year mother-to-child transmission rate of 15%. Although screening has improved over the past 5 years, fewer than three-quarters of infected pregnant women are receiving antiretroviral prophylaxis. Universal antiretroviral therapy for HIV-infected pregnant women will be essential in achieving Kenyans target to eliminate mother-to-child transmission to <5% by 2015.

Gaps in Adolescent Engagement in Antenatal Care and Prevention of Mother-to-Child HIV Transmission Services in Kenya

Background: Rates of pregnancy and HIV infection are high among adolescents. However, their engagement in prevention of mother-to-child HIV transmission (PMTCT) services is poorly characterized. We compared engagement in the PMTCT cascade between adult and adolescent mothers in Kenya. Methods: We conducted a nationally representative cross-sectional survey of mother–infant pairs attending 120 maternal child health clinics selected by probability proportionate to size sampling, with a secondary survey oversampling HIV-positive mothers in 30 clinics. Antenatal care (ANC) attendance, HIV testing, and antiretroviral (ARV) use were compared between adolescent (age ⩽19 years) and adult mothers using &khgr;2 tests and logistic regression. Results: Among 2521 mothers, 278 (12.8%) were adolescents. Adolescents were less likely than adults to be employed (16.5% vs. 37.9%), married (66.1% vs. 88.3%), have intended pregnancy (40.5% vs. 58.6%), or have disclosed their HIV status (77.5% vs. 90.7%) (P < 0.01 for all). Adolescents were less likely than adults to attend ≥4 ANC visits (35.2% vs. 45.6%, P = 0.002). This effect remained significant when adjusting for employment, household crowding, pregnancy intention, gravidity, and HIV status [adjusted odds ratio (95% confidence interval) = 0.54 (0.37 to 0.97), P = 0.001]. Among 2359 women without previous HIV testing, 96.1% received testing during pregnancy; testing levels did not differ between adolescents and adults. Among 288 HIV-positive women not on antiretroviral therapy before pregnancy, adolescents were less likely than adults to be on ARVs (65.0% vs. 85.8%, P = 0.01) or to have infants on ARVs (85.7% vs. 97.7%, P = 0.005). Conclusions: Adolescent mothers had poorer ANC attendance and uptake of ARVs for PMTCT. Targeted interventions are needed to improve retention of this vulnerable population in the PMTCT cascade.

Economic evaluation of an alternative drug to sulfadoxine-pyrimethamine as intermittent preventive treatment of malaria in pregnancy.

Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in HIV-negative women to avert malaria, while this relies on cotrimoxazole prophylaxis (CTXp) in HIV-positive women. Alternative antimalarials are required in areas where parasite resistance to antifolate drugs is high. The cost-effectiveness of IPTp with alternative drugs is needed to inform policy. Methods The cost-effectiveness of 2-dose IPTp-mefloquine (MQ) was compared with IPTp-SP in HIV-negative women (Benin, Gabon, Mozambique and Tanzania). In HIV-positive women the cost-effectiveness of 3-dose IPTp-MQ added to CTXp was compared with CTXp alone (Kenya, Mozambique and Tanzania). The outcomes used were maternal clinical malaria, anaemia at delivery and non-obstetric hospital admissions. The poor tolerability to MQ was included as the value of women’s loss of working days. Incremental cost-effectiveness ratios (ICERs) were calculated and threshold analysis undertaken. Results For HIV-negative women, the ICER for IPTp-MQ versus IPTp-SP was 136.30 US

Progress in Reversing the HIV Epidemic through Intensified Access to Antiretroviral Therapy: Results from a Nationally Representative Population-Based Survey in Kenya, 2012

(2012 US

Pharmacokinetics of mefloquine and its effect on sulfamethoxazole and trimethoprim steady-state blood levels in intermittent preventive treatment (IPTp) of pregnant HIV-infected women in Kenya

) (95%CI 131.41; 141.18) per disability-adjusted life-year (DALY) averted, or 237.78 US

High Prevalence of Abacavir-associated L74V/I Mutations in Kenyan Children Failing Antiretroviral Therapy

(95%CI 230.99; 244.57), depending on whether estimates from Gabon were included or not. For HIV-positive women, the ICER per DALY averted for IPTp-MQ added to CTXp, versus CTXp alone was 6.96 US

Rates and Predictors of Non-Adherence to Antiretroviral Therapy among HIV-Positive Individuals in Kenya: Results from the Second Kenya AIDS Indicator Survey, 2012

(95%CI 4.22; 9.70). In HIV-negative women, moderate shifts of variables such as malaria incidence, drug cost, and IPTp efficacy increased the ICERs above the cost-effectiveness threshold. In HIV-positive women the intervention remained cost-effective for a substantial (up to 21 times) increase in cost per tablet. Conclusions Addition of IPTp with an effective antimalarial to CTXp was very cost-effective in HIV-positive women. IPTp with an efficacious antimalarial was more cost-effective than IPTp-SP in HIV-negative women. However, the poor tolerability of MQ does not favour its use as IPTp. Regardless of HIV status, prevention of malaria in pregnancy with a highly efficacious, well tolerated antimalarial would be cost-effective despite its high price. Trials Registration ClinicalTrials.gov NCT 00811421; Pan African Trials Registry PACTR2010020001429343 and PACTR2010020001813440

Tuberculosis and HIV at the national level in Kenya: results from the Second Kenya AIDS Indicator Survey.

Background In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) called for 90% of persons living with HIV (PLHIV) to know their status, 90% of these to be on antiretroviral therapy (ART), and 90% of these to be virally suppressed by 2020 (90-90-90). It is not clear whether planned ART scale-up in countries whose eligibility criteria for ART initiation are based on recommendations from the 2013 World Health Organization treatment guidelines will be sufficient to meet UNAIDS new global targets. Materials and Methods Using data from a nationally representative population-based household survey of persons in Kenya we compared coverage and unmet need associated with HIV diagnosis, ART, and viral suppression among PLHIV aged 15–64 years in 2012 based on criteria outlined in the 2014 national ART guidelines and UNAIDS’ 90-90-90 goals. Estimates were weighted to account for sampling probability and nonresponse. Results Eight in ten PLHIV aged 15–64 years needed ART based on treatment eligibility. Need for treatment based on the national treatment policy was 97.4% of treatment need based on UNAIDS’ 90-90-90 goals, requiring an excess of 24,000 PLHIV to access treatment beyond those eligible for ART to achieve UNAIDS’ 90-90-90 treatment target. The gap in treatment coverage was high, ranging from 43.1% nationally to 52.3% in Nyanza among treatment-eligible PLHIV and 44.6% nationally to 52.4% in Nyanza among all PLHIV. Conclusion Maintaining the current pace of ART scale-up in Kenya will result in thousands of PLHIV unreached, many with high viral load and at-risk of transmitting infection to others. Careful strategies for reaching 90-90-90 will be instrumental in determining whether intensified access to treatment can be achieved to reach all who require ART.