Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. RESULTS: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.

Assessing Mobile Phone Access and Perceptions for Texting-Based mHealth Interventions Among Expectant Mothers and Child Caregivers in Remote Regions of Northern Kenya: A Survey-Based Descriptive Study.

BACKGROUND: With a dramatic increase in mobile phone use in low- and middle-income countries, mobile health (mHealth) has great potential to connect health care services directly to participants enrolled and improve engagement of care. Rural and remote global settings may pose both significant challenges and opportunities. OBJECTIVE: The objective of our study was to understand the demographics, phone usage and ownership characteristics, and feasibility among patients in rural and remote areas of Kenya of having text messaging (short messaging service, SMS)-based mHealth intervention for improvements in antenatal care attendance and routine immunization among children in Northern Kenya. METHODS: A survey-based descriptive study was conducted between October 2014 and February 2015 at 8 health facilities in Northern Kenya as part of a program to scale up an mHealth service in rural and remote regions. The study was conducted at 6 government health facilities in Isiolo, Marsabit, and Samburu counties in remote and northern arid lands (NAL). Two less remote health facilities in Laikipia and Meru counties in more populated central highlands were included as comparison sites. RESULTS: A total of 284 participants were surveyed; 63.4% (180/284) were from NAL clinics, whereas 36.6% (104/284) were from adjacent central highland clinics. In the NAL, almost half (48.8%, 88/180) reported no formal education and 24.4% (44/180) self-identified as nomads. The majority of participants from both regions had access to mobile phone: 99.0% (103/104) of participants from central highlands and 82.1% (147/180) of participants from NAL. Among those who had access to a phone, there were significant differences in network challenges and technology literacy between the 2 regions. However, there was no significant difference in the proportion of participants from NAL and central highlands who indicated that they would like to receive a weekly SMS text message from their health care provider (90.0% vs 95.0%; P=.52). Overall, 92.0% (230/250) of participants who had access to a telephone said that they would like to receive a weekly SMS text message from their health care provider. Most phone users already spent the equivalent of 626 SMS text messages on mobile credit for personal use. CONCLUSIONS: Despite the remoteness of northern Kenya's NAL, the results indicate that the majority of pregnant women or care givers attending the maternal, newborn, and child health clinics have access to mobile phone and would like to receive text messages from their health care provider. mHealth programs, if designed appropriately for these settings, may be an innovative way for engaging women in care for improved maternal and newborn child health outcomes in order to achieve sustainable development goals.

Identifying and addressing barriers to uptake of voluntary medical male circumcision in Nyanza, Kenya among men 18-35: a qualitative study.

BACKGROUND: Uptake of VMMC among adult men has been lower than desired in Nyanza, Kenya. Previous research has identified several barriers to uptake but qualitative exploration of barriers is limited and evidence-informed interventions have not been fully developed. This study was conducted in 2012 to 1) increase understanding of barriers to VMMC and 2) to inform VMMC rollout through the identification of evidence-informed interventions among adult men at high risk of HIV in Nyanza Province, Kenya. METHODS: Focus groups (n = 8) and interviews were conducted with circumcised (n = 8) and uncircumcised men (n = 14) from the two districts in Nyanza, Kenya. Additional interviews were conducted with female partners (n = 20), health providers (n = 12), community leaders (n = 12) and employers (n = 12). Interview and focus group guides included questions about individual, interpersonal and societal barriers to VMMC uptake and ways to overcome them. Inductive thematic coding and analysis were conducted through a standard iterative process. RESULTS: Two primary concerns with VMMC emerged 1) financial issues including missing work, losing income during the procedure and healing and family survival during the recovery period and 2) fear of pain during and after the procedure. Key interventions to address financial concerns included: a food or cash transfer, education on saving and employer-based benefits. Interventions to address concerns about pain included refining the content of demand creation and counseling messages about pain and improving the ways these messages are delivered. CONCLUSIONS: Men need accurate and detailed information on what to expect during and after VMMC regarding both pain and time away from work. This information should be incorporated into demand creation activities for men considering circumcision. Media content should frankly and correctly address these concerns. Study findings support scale up and/or further improvement of these ongoing educational programs and specifically targeting the demand creation period.

Systematic Monitoring of Voluntary Medical Male Circumcision Scale-up: adoption of efficiency elements in Kenya, South Africa, Tanzania, and Zimbabwe.

BACKGROUND: SYMMACS, the Systematic Monitoring of the Voluntary Medical Male Circumcision Scale-up, tracked the implementation and adoption of six elements of surgical efficiency-use of multiple surgical beds, pre-bundled kits, task shifting, task sharing, forceps-guided surgical method, and electrocautery--as standards of surgical efficiency in Kenya, South Africa, Tanzania, and Zimbabwe. METHODS AND FINDINGS: This multi-country study used two-staged sampling. The first stage sampled VMMC sites: 73 in 2011, 122 in 2012. The second stage involved sampling providers (358 in 2011, 591 in 2012) and VMMC procedures for observation (594 in 2011, 1034 in 2012). The number of VMMC sites increased significantly between 2011 and 2012; marked seasonal variation occurred in peak periods for VMMC. Countries adopted between three and five of the six elements; forceps-guided surgery was the only element adopted by all countries. Kenya and Tanzania routinely practiced task-shifting. South Africa and Zimbabwe used pre-bundled kits with disposable instruments and electrocautery. South Africa, Tanzania, and Zimbabwe routinely employed multiple surgical bays. CONCLUSIONS: SYMMACS is the first study to provide data on the implementation of VMMC programs and adoption of elements of surgical efficiency. Findings have contributed to policy change on task-shifting in Zimbabwe, a review of the monitoring system for adverse events in South Africa, an increased use of commercially bundled VMMC kits in Tanzania, and policy dialogue on improving VMMC service delivery in Kenya. This article serves as an overview for five other articles following this supplement.

Women's roles in voluntary medical male circumcision in Nyanza Province, Kenya.

Women are an important audience for voluntary medical male circumcision (VMMC) communication messages so that they know that VMMC provides only partial protection against HIV. They may also be able to influence their male partners to get circumcised and practice other HIV protective measures after VMMC. This study was conducted in two phases of qualitative data collection. Phase 1 used in-depth interviews to explore women's understanding of partial protection and their role in VMMC. Phase 2 built on the findings from the Phase 1, using focus groups to test VMMC communication messages currently used in Nyanza Province and to further explore women's roles in VMMC. Sixty-four sexually active women between the ages of 18 and 35 participated. In Phase 1, all women said they had heard of partial protection, though some were not able to elaborate on what the concept means. When women in Phase 2 were exposed to messages about partial protection, however, participants understood the messages well and were able to identify the main points. In Phases 1 and 2, many participants said that they had discussed VMMC with their partner, and for several, it was a joint decision for the man to go for VMMC. These findings suggest that current VMMC messaging is reaching women, though communications could more effectively target women to increase their ability to communicate about partial HIV protection from VMMC. Also, women seem to be playing an important role in encouraging men to get circumcised, so reaching out to women could be a valuable intervention strategy for increasing VMMC uptake and promoting use of other HIV protective measures after VMMC.

Voluntary medical male circumcision: translating research into the rapid expansion of services in Kenya, 2008-2011.

Since the World Health Organization and the Joint United Nations Programme on HIV/AIDS recommended implementation of medical male circumcision (MC) as part of HIV prevention in areas with low MC and high HIV prevalence rates in 2007, the government of Kenya has developed a strategy to circumcise 80% of uncircumcised men within five years. To facilitate the quick translation of research to practice, a national MC task force was formed in 2007, a medical MC policy was implemented in early 2008, and Nyanza Province, the region with the highest HIV burden and low rates of circumcision, was prioritized for services under the direction of a provincial voluntary medical male circumcision (VMMC) task force. The government's early and continuous engagement with community leaders/elders, politicians, youth, and women's groups has led to the rapid endorsement and acceptance of VMMC. In addition, several innovative approaches have helped to optimize VMMC scale-up. Since October 2008, the Kenyan VMMC program has circumcised approximately 290,000 men, mainly in Nyanza Province, an accomplishment made possible through a combination of governmental leadership, a documented implementation strategy, and the adoption of appropriate and innovative approaches. Kenya's success provides a model for others planning VMMC scale-up programs.

Reduction of the efficacy of antifolate antimalarial therapy by folic acid supplementation.

Malaria and anemia are common conditions in patients presenting to outpatient clinics in Kenya. Anemia is usually due to malaria infection with underlying micronutrient deficiency. Iron therapy has been shown to enhance recovery from anemia in children with malaria, without affecting malaria treatment. Iron and folic acid are often prescribed together for anemic individuals. Until recently in Kenya, the drug of first choice for non-severe malaria was sulfadoxine-pyrimethamine (SP), an antifolate antimalarial drug. In this study, 303 patients of all ages with anemia and uncomplicated Plasmodium falciparum malaria attending an outpatient clinic in an area of seasonal malaria were treated with SP and iron, and were randomized to receive folic acid. Parasite clearance rates were measured using a survival analysis plot for both parasitologic and clinical failure. There was a significant reduction in the efficacy of SP in patients taking standard therapeutic doses of folic acid using the survival curve for parasitologic failure (P < 0.0001), but no difference for clinical failure (P = 0.7008). Folic acid supplementation did not enhance recovery from anemia.