Randomized trial evaluating an mHealth intervention for the early community-based detection and follow-up of cutaneous leishmaniasis in rural Colombia.

BACKGROUND: In Latin America, cutaneous leishmaniasis primarily affects dispersed rural communities, that have limited access to the public health system and medical attention. Mobile health (mHealth) strategies have shown potential to improve clinical management and epidemiological surveillance of neglected tropical diseases, particularly those of the skin. METHODS: The Guaral +ST app for Android was designed to monitor cutaneous leishmaniasis treatment and assess therapeutic response. We carried out a randomized trial in the coastal municipality of Tumaco in southwestern Colombia, with parallel arms comparing a) follow-up aided by the app to b) standard institution-based follow-up. Treatment was prescribed according to national guidelines. Follow-up of therapeutic response was scheduled at the end of treatment and at 7, 13 and 26 weeks after the start of treatment. The primary endpoint was the proportion of participants who were monitored at or around week 26, allowing outcome and effectiveness of treatment to be determined. RESULTS: Follow-up of treatment and outcome assessment was achieved in significantly more patients in the intervention arm than the controls, Of the 75 participants in the two randomized arms, 74 had information on whether or not treatment was followed and outcome determined at or around week 26. Among these, 26/49 (53.1%) were evaluated in the intervention arm, and none (0/25, 0%) in the control arm (difference = 53.1%, 95% confidence interval 39.1-67.0%, p<0.001). Of the 26 participants evaluated at or around week 26 in the intervention arm, 22 (84.6%) had cured. There were no serious adverse events, nor events of severe intensity among patients monitored by CHW using the app. CONCLUSION: This study provides proof of concept for mHealth to monitor treatment of CL in remote and complex settings, deliver improved care and to provide information to the health system on the effectiveness of treatment as it is delivered to affected populations. CLINICAL TRIAL REGISTRATION: ISRCTN54865992.

Adaptation and performance of a mobile application for early detection of cutaneous leishmaniasis.

BACKGROUND: Detection and management of neglected tropical diseases such as cutaneous leishmaniasis present unmet challenges stemming from their prevalence in remote, rural, resource constrained areas having limited access to health services. These challenges are frequently compounded by armed conflict or illicit extractive industries. The use of mobile health technologies has shown promise in such settings, yet data on outcomes in the field remain scarce. METHODS: We adapted a validated prediction rule for the presumptive diagnosis of CL to create a mobile application for use by community health volunteers. We used human-centered design practices and agile development for app iteration. We tested the application in three rural areas where cutaneous leishmaniasis is endemic and an urban setting where patients seek medical attention in the municipality of Tumaco, Colombia. The application was assessed for usability, sensitivity and inter-rater reliability (kappa) when used by community health volunteers (CHV), health workers and a general practitioner, study physician. RESULTS: The application was readily used and understood. Among 122 screened cases with cutaneous ulcers, sensitivity to detect parasitologically proven CL was >95%. The proportion of participants with parasitologically confirmed CL was high (88%), precluding evaluation of specificity, and driving a high level of crude agreement between the app and parasitological diagnosis. The chance-adjusted agreement (kappa) varied across the components of the risk score. Time to diagnosis was reduced significantly, from 8 to 4 weeks on average when CHV conducted active case detection using the application, compared to passive case detection by health facility-based personnel. CONCLUSIONS: Translating a validated prediction rule to a mHealth technology has shown the potential to improve the capacity of community health workers and healthcare personnel to provide opportune care, and access to health services for underserved populations. These findings support the use of mHealth tools for NTD research and healthcare.

The feasibility of establishing parent support groups for children with congenital Zika syndrome and their families: a mixed-methods study.

Background: The 2015 - 2016 Zika epidemic highlighted gaps in health and social care services for parents of children with developmental disabilities. In response, we developed the 'Juntos' intervention, a 10 week community-based early intervention support group for parents of children with congenital Zika syndrome (CZS). The intervention's components include participatory learning sessions, practical skill acquisition, peer support, and psychological support, aiming to improve caregiver's knowledge and confidence in caring for their children. This study aimed to evaluate the feasibility of implementing 'Juntos' in Colombia. Methods: Two facilitators delivered 'Juntos' to four groups of 8-10 caregivers between 2017 and 2018. One researcher observed each group. Data were collected from: observation notes from 40 sessions, focus group discussions held after each session, pre- post intervention questionnaires with 34 caregivers, and semi-structured interviews conducted with four facilitators, 12 caregivers and three stakeholders. We used the Bowen framework in data analysis. Results: The feasibility evaluation revealed that 'Juntos' was highly acceptable and in demand among the target population. The intervention was predominantly delivered with fidelity. Practicality was facilitated by providing transport costs and selecting convenient locations. Additional organisational and social media support was required for successful implementation. Community health worker training may support integration and the established groups could facilitate programme expansion. However, participants perceived lack of prioritisation as a limitation within existing health systems. Participants' knowledge and confidence to care for their child improved after programme enrolment. Conclusion: The 'Juntos' intervention demonstrated high acceptability, demand, and practicality in supporting parents of children with CZS in Colombia. However, its implementation faces challenges due to existing gaps in health system support for children with CZS.

HLA-B*57:01 allele prevalence in treatment-Naïve HIV-infected patients from Colombia.

BACKGROUND: The HLA-B*57:01 allele is associated with a hypersensitivity reaction to abacavir. Due to the lack of knowledge of HLA-B*57:01 prevalence in Colombia, routine screening is not performed and is not recommended by the national guidelines. We aimed to determine the prevalence of HLA-B*57:01 in HIV population from Colombia. METHODS: This cross-sectional study included naïve HIV-infected adults from 13 cities of the country. The presence of HLA-B*57:01 was determined by using SSP-PCR in blood samples. Prevalence rates were stratified by sex, race, and region of origin. RESULTS: HLA-B*57:01 allele prevalence in Colombian HIV-infected individuals was 2.7%. When stratifying for the race, the prevalence was 4% for whites, 2.6% for other race (mainly mestizo), and 1.9% for Afro-Colombians. The prevalence varied from 0% up to 11.4% depending on the department of origin. The highest prevalence rates were found in Caldas (11.4%), Antioquia (5%), Risaralda (4.8%), and Valle del Cauca (4.3%). When distributed by country zones, the central, with a racial predominance of Caucasians and mestizos, was the highest (6.0%, 0R = 4.1, CI 1.2-12.8, p = 0,016). CONCLUSIONS: The overall prevalence of HLA-B*57:01 in Colombia was lower than the reported rates for other Latin American countries such as Brazil, Costa Rica, and Argentina, but similar in comparison to Chile and Mexico. The diversity in the racial and ethnic heritage shown in our data supports the recommendation to implement routine screening for the HLA-B*57:01 allele before initiation of abacavir-containing antiretroviral therapy in the Colombian HIV management guidelines.

Developing mobile health applications for neglected tropical disease research.

Mobile applications (apps) can bring health research and its potential downstream benefits closer to underserved populations. Drawing on experience developing an app for detecting and referring cases of cutaneous leishmaniasis in Colombia, called Guaral/app, we review key steps in creating such mobile health (mHealth) tools. These require consideration of the sociotechnical context using methods such as systems analysis and human-centered design (HCD), predicated on engagement and iteration with all stakeholders. We emphasize usability and technical concerns and describe the interdependency of technical and human considerations for mHealth systems in rural communities.

[Educating health workers is key in congenital syphilis elimination in Colombia].

INTRODUCTION: Colombia promotes the diagnosis and treatment of gestational syphilis in a single visit using rapid diagnostic tests to prevent mother-to-child transmission. Additionally, integrated health programs pursue the coordinated prevention of mother-to-child transmission of syphilis/HIV. OBJECTIVE: To identify knowledge gaps among health workers in the prevention of mother-to-child transmission of syphilis/HIV and to provide recommendations to support these programs. MATERIALS AND METHODS: We conducted a descriptive study based on 306 surveys of health workers in 39 health institutions in the city of Cali. Surveys inquired about planning, management and implementation of services for pregnant women, clinical knowledge of HIV/syphilis rapid diagnostic tests, and prior training. RESULTS: Knowledge deficits in the management of gestational syphilis were detected among the surveyed health workers, including physicians. Rapid tests for syphilis are currently used in clinical laboratories in Cali, however, procedural deficiencies were observed in their use, including quality control assurance. During the two years prior to the survey, training of health workers in the prevention of mother-to-child transmission of syphilis/HIV had been limited. Health workers are interested in identifying and treating gestational syphilis in a single event, in using rapid diagnostic tests and in receiving training. CONCLUSIONS: Intensive training targeting health workers, policy/decision makers and academic groups is needed to ensure adequate implementation of new strategies for the prevention of mother-to-child transmission of syphilis/HIV.

La educación del personal de salud: clave para la eliminación de la sífilis congénita en Colombia / Educating health workers is key in congenital syphilis elimination in Colombia

Resumen Introducción. Para la prevención de la transmisión materno-infantil de la sífilis en Colombia, se promueve el diagnóstico y el tratamiento en una sola consulta mediante el uso de pruebas de diagnóstico rápido, así como programas de eliminación conjunta de la transmisión materno-infantil de la sífilis y el HIV. Objetivo. Detectar los vacíos de capacitación del personal de salud en torno a la prevención de la transmisión materno-infantil de la sífilis y el HIV, y hacer recomendaciones para mejorar los programas. Materiales y métodos. Se hizo un estudio descriptivo mediante 306 encuestas hechas al personal de salud de 39 instituciones de Cali. Se indagó sobre la planeación, la gestión y la ejecución de los servicios ofrecidos a las mujeres gestantes, los conocimientos clínicos sobre la sífilis, el HIV y las pruebas rápidas, así como sobre las capacitaciones recibidas. Resultados. Se encontraron deficiencias en el conocimiento del manejo de la sífilis gestacional entre el personal de salud, incluidos los médicos. Las pruebas de diagnóstico rápido para sífilis se utilizan en los laboratorios de la ciudad, pero se detectaron fallas en su uso adecuado, especialmente en el control de calidad. La capacitación en temas de prevención de la transmisión materno-infantil de la sífilis y el HIV había sido escasa en los dos años anteriores. El personal de salud expresó su interés por diagnosticar y tratar la sífilis gestacional en una sola consulta, usar las pruebas de diagnóstico rápido y asistir a actividades de capacitación. Conclusiones. Se requiere la capacitación intensiva del personal de salud, de quienes toman las decisiones y de los grupos académicos, para lograr una adecuada implementación de las nuevas estrategias de prevención de la transmisión materno-infantil de la sífilisy el HIV.

Abstract Introduction: Colombia promotes the diagnosis and treatment of gestational syphilis in a single visit using rapid diagnostic tests to prevent mother-to-child transmission. Additionally, integrated health programs pursue the coordinated prevention of mother-to-child transmission of syphilis/HIV. Objective: To identify knowledge gaps among health workers in the prevention of mother-to-child transmission of syphilis/HIV and to provide recommendations to support these programs. Materials and methods: We conducted a descriptive study based on 306 surveys of health workers in 39 health institutions in the city of Cali. Surveys inquired about planning, management and implementation of services for pregnant women, clinical knowledge of HIV/syphilis rapid diagnostic tests, and prior training. Results: Knowledge deficits in the management of gestational syphilis were detected among the surveyed health workers, including physicians. Rapid tests for syphilis are currently used in clinical laboratories in Cali, however, procedural deficiencies were observed in their use, including quality control assurance. During the two years prior to the survey, training of health workers in the prevention of mother-to-child transmission of syphilis/HIV had been limited. Health workers are interested in identifying and treating gestational syphilis in a single event, in using rapid diagnostic tests and in receiving training. Conclusions: Intensive training targeting health workers, policy/decision makers and academic groups is needed to ensure adequate implementation of new strategies for the prevention of mother-to-child transmission of syphilis/HIV.

Parasitological Confirmation and Analysis of Leishmania Diversity in Asymptomatic and Subclinical Infection following Resolution of Cutaneous Leishmaniasis.

BACKGROUND: The contribution of individuals with subclinical infection to the transmission and endemicity of cutaneous leishmaniasis (CL) is unknown. Immunological evidence of exposure to Leishmania in residents of endemic areas has been the basis for defining the human population with asymptomatic infection. However, parasitological confirmation of subclinical infection is lacking. METHODS: We investigated the presence and viability of Leishmania in blood and non-invasive mucosal tissue samples from individuals with immunological evidence of subclinical infection in endemic areas for CL caused by Leishmania (Viannia) in Colombia. Detection of Leishmania kDNA was conducted by PCR-Southern Blot, and parasite viability was confirmed by amplification of parasite 7SLRNA gene transcripts. A molecular tool for genetic diversity analysis of parasite populations causing persistent subclinical infection based on PCR amplification and sequence analysis of an 82bp region between kDNA conserved blocks 1 and 2 was developed. PRINCIPAL FINDINGS: Persistent Leishmania infection was demonstrated in 40% (46 of 114) of leishmanin skin test (LST) positive individuals without active disease; parasite viability was established in 59% of these (27 of 46; 24% of total). Parasite burden quantified from circulating blood monocytes, nasal, conjunctival or tonsil mucosal swab samples was comparable, and ranged between 0.2 to 22 parasites per reaction. kDNA sequences were obtained from samples from 2 individuals with asymptomatic infection and from 26 with history of CL, allowing genetic distance analysis that revealed diversity among sequences and clustering within the L. (Viannia) subgenus. CONCLUSIONS: Our results provide parasitological confirmation of persistent infection among residents of endemic areas of L. (Viannia) transmission who have experienced asymptomatic infection or recovered from CL, revealing a reservoir of infection that potentially contributes to the endemicity and transmission of disease. kDNA genotyping establishes proof-of-principle of the feasibility of genetic diversity analysis in previously inaccessible and unexplored parasite populations in subclinically infected individuals.

First report of Warileya rotundipennis (Psychodidae: Phlebotominae) naturally infected with Leishmania (Viannia) in a focus of cutaneous leishmaniasis in Colombia.

The expansion of transmission of cutaneous leishmaniasis from sylvatic ecosystems into peri-urban and domestic settings has occurred as sand flies have adapted to anthropogenic environmental modifications. Assessment of the intradomiciliary presence of sand flies in households of the settlement "La Cabaña", in the Department of Risaralda, Colombia, revealed an abundance of Warileya rotundipennis. This unexpected observation motivated further analyses to evaluate the participation of this species in the transmission of cutaneous leishmaniasis. Collections using CDC light traps were conducted during two consecutive nights in May and August 2011.The total of 667 sand flies collected were classified into five species: W. rotundipennis (n=654; 98.05%), Nyssomyia trapidoi (n=7; 1.04%); Lutzomyia (Helcocyrtomyia) hartmanni (n=3; 0.44%); Lutzomyia lichyi (n=2; 0.29%) and Psychodopygus panamensis (n=1; 0.14%). The striking predominance of W. rotundipennis within households during both wet (May) and dry (August) seasons, anthropophilic behavior demonstrated by human blood in 95.23% (60/63) evaluable blood-engorged specimens, and natural infection (5/168-3%) with genetically similar parasites of the Leishmania (Viannia) subgenus observed in a patient in this community, support the involvement of W. rotundipennis in the domestic transmission of cutaneous leishmaniasis in "La Cabaña".

Treatment failure and miltefosine susceptibility in dermal leishmaniasis caused by Leishmania subgenus Viannia species.

Treatment failure and parasite drug susceptibility in dermal leishmaniasis caused by Leishmania (Viannia) species are poorly understood. Prospective evaluation of drug susceptibility of strains isolated from individual patients before drug exposure and at clinical failure allows intrinsic and acquired differences in susceptibility to be discerned and analyzed. To determine whether intrinsic susceptibility or loss of susceptibility to miltefosine contributed to treatment failure, we evaluated the miltefosine susceptibility of intracellular amastigotes and promastigotes of six Leishmania (Viannia) braziliensis and six Leishmania (Viannia) panamensis strains isolated sequentially, at diagnosis and treatment failure, from two children and four adults ≥55 years old with concurrent conditions. Four patients presented only cutaneous lesions, one had mucosal disease, and one had disseminated mucocutaneous disease. Expression of the Leishmania drug transporter genes abca2, abca3, abcc2, abcc3, abcg4, abcg6, and LbMT was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Intracellular amastigotes (median 50% effective concentration [EC50], 10.7 µmol/liter) were more susceptible to miltefosine than promastigotes (median EC50, 55.3 µmol/liter) (P < 0.0001). Loss of susceptibility at failure, demonstrated by a miltefosine EC50 of >32 µmol/liter (the upper limit of intracellular amastigote assay), occurred in L. panamensis infection in a child and in L. braziliensis infection in an adult and was accompanied by decreased expression of the miltefosine transporter LbMT (LbMT/ß-tubulin, 0.42- to 0.26-fold [P = 0.039] and 0.70- to 0.57-fold [P = 0.009], respectively). LbMT gene polymorphisms were not associated with susceptibility phenotype. Leishmania ABCA3 transporter expression was inversely correlated with miltefosine susceptibility (r = -0.605; P = 0.037). Loss of susceptibility is one of multiple factors involved in failure of miltefosine treatment in dermal leishmaniasis.

Gestational and congenital syphilis epidemic in the Colombian Pacific Coast.

BACKGROUND: Congenital syphilis (CS) is a major global public health problem. Buenaventura, a socioeconomically deprived municipality in the Colombian Pacific Coast, accounts for 6.6% of all CS cases in Colombia. To begin to understand the main reasons for the high rates of the disease in Buenaventura, we conducted a retrospective electronic health record analysis of all infants admitted with CS during the first 7 months of 2011 to the Hospital Departamental de Buenaventura, the city's main birthing hospital. METHODS: The diagnosis of gestational syphilis and CS was based on a predefined Colombian public health service algorithm. Clinical, laboratory, and sociodemographic parameters for all infants studied, including maternal access to prenatal care, syphilis serologic diagnosis, and adequacy of penicillin treatment, were abstracted and analyzed. RESULTS: A total of 89 infants met the case definition for CS. Most mothers (80%) were affiliated with government-regulated or private health care insurance plans. While 64 (70%) of 92 attended at least 1 antenatal care visit and 59 of these 64 (84%) were screened for syphilis, only 5 (8%) of 59 received appropriate antibiotic therapy. Although most infants were asymptomatic at birth, prematurity (15/82) was common. Two infants died in the neonatal period, and 5 pregnancies ended in stillbirth. CONCLUSIONS: Our findings confirm that Buenaventura has a very high incidence of CS and demonstrate that existing antenatal care gestational syphilis programs are flawed. Prevention strategies should emphasize enhanced early syphilis screening in pregnancy, preferably through the implementation of point-of-care testing in the community and same-day treatment with at least 1 dose of penicillin.

Possible links between sickle cell crisis and pentavalent antimony.

For over 60 years, pentavalent antimony (Sb(v)) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sb(v) revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sb(v), and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sb(v) caused the SCC.

Noninferiority of miltefosine versus meglumine antimoniate for cutaneous leishmaniasis in children.

BACKGROUND: Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. METHODS: A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2-12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8-2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). RESULTS: Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%-28.7%) for miltefosine and 31% (98% CI, 16.9%-45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, -4.5% to 32%) (P = .04). Adverse events were mild for both treatments. CONCLUSIONS: Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. CLINICAL TRIAL REGISTRATION: NCT00487253.

Alteraciones metabólicas con terapia antirretroviral altamente efectiva en niños positivos para VIH, Cali, Colombia / Metabolic alterations with anti-retroviral highly effective therapy in positive children for VIH, Cali, Colombia

Objetivos: describir las alteraciones metabólicas en niños con diagnóstico de VIH y en tratamiento con terapia antirretroviral altamente efectiva (Highly Active Antiretroviral Therapy, HAART). Métodos: se realizó una primera fase descriptiva de los valores de lípidos y glucemia en una cohorte de niños positivos para VIH. De una clínica pediátrica se reclutaron, entre junio de 2003 y junio de 2005, niños mayores de un mes y menores de 16 años en terapia HAART. Estos resultados se compararon con valores de la población. En una segunda fase, se estudió la densidad ósea en estos niños, utilizando DEXA (dual energy X-ray absorptiometry) y antropometría, y se comparó la de controles sanos. Resultados: se incluyeron 38 niños positivos para VIH. En 59,5% de los niños se clasificaron con displidemia. Al compararlo con la población de referencia, el grupo positivo para VIH presentó una prevalencia mayor de hipertrigliceridemia y HDLc (highdensity lipoprotein) anormalmente bajo. Tomando en cuenta la variación por edad, los valores de colesterol total y LDLc (lowdensity lipoprotein), mostraron un aumento en el grupo que recibía inhibidores de proteasa (IP) contra el que no. La diferencia del puntaje Z de BMD (bone mineral density) entre los grupos fue de 0,56 (IC95%: 0,1- 1,0), teniendo un menor puntaje Z el grupo positivo para VIH. El puntaje Z de la densidad de masa ósea mostró un declive con el tiempo de exposición, que no fue evidente en el grupo control. Conclusiones: encontramos alteraciones en los lípidos similares a las descritas en el adulto seropositivo. En el grupo con IP se encontraron alteraciones del colesterol que cambiaban según la edad. Se encontró una pérdida de la densidad ósea, progresiva con el tiempo de exposición e independiente de la edad. Consideramos que esta relación podría ser de origen multifactorial, incluyendo los efectos de la infección y del tratamiento.

Objectives: our goal is to describe metabolic alterations in children with HIV and under highly effective anti-retroviral treatment (HAART). Methodology: a first descriptive phase of lipid levels and glucemia was carried out in a cohort of HIV positive children. In a paediatric hospital, children >1 month and <16 years old under HAART were recruited from June, 2003 to June, 2005. The results were compared to population values. During the second phase, bone density was studied in these children using DEXA and anthropometric values and compared to healthy control subjects. Results: thirty eight positive children were included. 59.5% of the children were classified as having dyslipidemia. Upon comparison to the reference population, the HIV(+) group showed larger hypertrigliceridemia prevalence and abnormally low cHDL. Taking into account age variations, total colesterol values and cLDL showed increase in the group that received PI against those that did not. The difference of the BMD Z-Score among the groups was 0,56 (CI95%: 0.1, 1.0), the HIV(+) group having a smaller Z-Score. The bone mass density Z-Score showed a decline according exposition time, which was not evident in the control group. Conclusions: alterations in lipids similar to those described in the seropositive adult were found. The group with PI showed cholesterol alterations that changed according to age. Progressive bone density loss according to exposition time was found regardless of age. It is considered that this relationship could have multifactorial origin, including infection and treatment effects.

Immunogenicity and reactogenicity of DTPw-HB/Hib vaccine administered to colombian infants after a birth dose of hepatitis B vaccine.

OBJECTIVE: To evaluate, in an open study, the immunogenicity, safety and reactogenicity of a birth dose of hepatitis B vaccine followed by a three-dose course of diphtheria-tetanus whole-cell pertussis-hepatitis B vaccine, extemporaneously mixed with Haemophilus influenzae b (Hib) vaccine. METHODS: At 2, 4 and 6 months of age, a single group of 120 Colombian infants were enrolled in this study to receive a regimen consisting of three doses of the combination vaccine following a dose of hepatitis B vaccine at birth. RESULTS: Seroprotection/vaccine response rates to all vaccine antigens was 98-100% 1 month after completion of the full vaccination course. The vaccine had an acceptable reactogenicity profile and the incidence of reported local and general symptoms decreased with the administration of subsequent vaccine doses. CONCLUSION: The mixed DTPw-HB/Hib vaccine was safe and well-tolerated, with high immunogenicity against all component antigens. Compared with previous studies, reactogenicity did not increase with the additional dose of hepatitis B vaccine given at birth. The DTPw-HB/Hib combination can be used to provide primary vaccination of infants who have already received a first dose of hepatitis B vaccine at birth.