Scaling up isoniazid preventive therapy in Zimbabwe: has operational research influenced policy and practice?

Setting: Following the operational research study conducted during the isoniazid preventive therapy (IPT) pilot phase in Zimbabwe, recommendations for improvement were adopted by the national antiretroviral therapy (ART) programme. Objectives: To compare before (January 2013-June 2014) and after the recommendations (July 2014-December 2015), the extent of IPT scale-up and IPT completion rates, and after the recommendations the risk factors for IPT non-completion, in 530 ART clinics. Design: Retrospective cohort study. Results: People living with the human immunodeficiency virus newly initiating IPT increased every quarter (Q), from 585 in Q 1, 2013 to 4246 in Q 4, 2015, with 5648 new IPT initiations in the 18 months before the recommendations compared to 20 513 in the 18 months after the recommendations were made. The number of ART clinics initiating IPT increased from 10 (2%) in Q 1, 2013 to 198 (37%) in Q 4, 2015. Overall IPT completion rates were 89% in the post-recommendation period compared with 81% in the pilot phase (P < 0.001). After adjusting for confounders, being lost to follow-up from clinic review visits 1 year prior to IPT initiation was associated with a higher risk of not completing IPT, while having synchronised IPT and ART resupplies was associated with a lower risk. Conclusions: Implementation of recommendations from the initial operational research study have improved IPT scale-up in Zimbabwe.

Contexte : A la suite d'une recherche opérationnelle réalisée pendant la phase pilote du traitement préventif par isoniazide (TPI) au Zimbabwe, des recommandations visant à une expansion ont été adoptées par le programme national de traitement antirétroviral (TAR).Objectifs : Dans 530 centres de TAR, comparer avant (janvier 2013 à juin 2014) et après les recommandations (juillet 2014 à décembre 2015), le degré d'expansion du TPI et ses taux d'achèvement, et après les recommandations, examiner les facteurs de risque de non achèvement.Schéma : Cohorte rétrospective.Résultats : Le nombre des personnes vivant avec le virus de l'immunodéficience humaine démarrant le TPI ont augmenté chaque trimestre de 585 pendant le premier trimestre de 2013 à 4246 pendant le quatrième trimestre de 2015, avec 5648 nouvelles mises en route du TPI dans les 18 mois avant les recommandations et 20 513 dans la période de 18 mois après les recommandations. Le nombre de centres de TAR mettant en route le TPI a augmenté de 10 (2%) au premier trimestre 2013 à 198 (37%) au quatrième trimestre 2015. Les taux d'ensemble d'achèvement du TPI ont été de 89% dans la période suivant les recommandations comparés à 81% pendant la phase pilote (P < 0,001). Après ajustement sur les facteurs de confusion, le fait d'être perdus de vue des consultations de suivi au centre 1 an avant la mise en route du TPI a été associé à un risque plus élevé de non achèvement du TPI, tandis que la synchronisation du renouvellement des fournitures du TPI et du TAR a été associée à un risque plus faible.Conclusions: Les recommandations émanant de la recherche opérationnelle initiale ont amélioré l'expansion du TPI au Zimbabwe.

Marco de referencia: El programa nacional de tratamiento antirretrovírico (TAR), tras una investigación operativa realizada durante la fase preliminar de aplicación del tratamiento preventivo con isoniazida (TPI) en Zimbabwe, adoptó las medidas de mejoramiento que se recomendaban.Objetivos: Comparar en 530 consultorios de suministro del TAR la magnitud de la ampliación de escala del TPI y las tasas de compleción del mismo, antes (de enero del 2013 a junio del 2014) y después (de julio del 2014 a diciembre del 2015) de la puesta en práctica de las recomendaciones, y después de su adopción, examinar los factores de riesgo de no completar el TPI.Método: Fue este un estudio de cohortes retrospectivo.Resultados: El número de personas infectadas por el virus de la inmunodeficiencia humana que iniciaban el TPI aumentó en cada trimestre, de 585 en el primer trimestre del 2013 a 4246 en el cuarto trimestre del 2015; se contabilizaron 5648 nuevos inicios del TPI en los 18 meses que precedieron la aplicación de las recomendaciones y 20 513 casos en los 18 meses que siguieron a la puesta en práctica de las mismas. El número de consultorios de TAR que iniciaban el TPI aumentó de 10 (2%) en el primer trimestre del 2013 a 198 (37%) en el cuarto trimestre del 2015. La tasa de compleción global del TPI fue 89% en el período posterior a las recomendaciones, comparada con 81% en la fase preliminar (P < 0,001). Tras corregir con respecto a las variables de confusión, la pérdida durante el seguimiento en las citas de control en el consultorio durante el año anterior a la iniciación del TPI se asoció con un mayor riesgo de no completar el TPI; al contrario, la sincronización del suministro del TPI y el TAR se asoció con una disminución del riesgo.Conclusión: La aplicación de las medidas recomendadas durante la investigación operativa inicial ha mejorado la ampliación de escala del suministro del TPI en Zimbabwe.

Routine implementation of isoniazid preventive therapy in HIV-infected patients in seven pilot sites in Zimbabwe.

Setting: Seven pilot sites in Zimbabwe implementing 6 months of isoniazid preventive therapy (IPT) for people living with the human immunodeficiency virus (PLHIV). Objectives: To determine, among PLHIV started on IPT, the completion rates for a 6-month course of IPT and factors associated with non-adherence. Design: A retrospective cohort study. Results: Of 578 patients, 466 (81%) completed IPT. Of the 112 patients who failed to complete IPT, 69 (60%) were lost to follow-up, 30 (27%) stopped treatment with no documented reasons, 8 (7%) developed toxicity/adverse reactions, 5 (5%) were documented as having drug stock-outs and the remainder transferred out or refused to continue treatment. Currently being on antiretroviral therapy (ART) (aOR 0.09, 95%CI 0.03-0.28) and receiving a ⩾2 month supply of isoniazid at the start of treatment were associated with a lower risk of not completing IPT, while missing clinic visits prior to starting IPT (aOR 5.25, 95%CI 2.10-13.14) was associated with a higher risk of non-completion. Conclusion: IPT completion rates in seven pilot sites of Zimbabwe were comparatively high, showing that IPT roll-out in public health facilities is feasible. Enhanced adherence counselling or active tracing among pre-ART patients and those with a history of loss to follow-up may improve IPT completion rates, along with synchronising IPT and ART resupplies.

Contexte : Sept sites pilotes au Zimbabwe mettant en œuvre le traitement préventif par isoniazide de 6 mois (TPI) pour les personnes vivant avec le virus de l'immunodéficience humaine VIH (PVVIH).Objectifs : Déterminer, parmi les PVVIH ayant mis en route le TPI : les taux d'achèvement du traitement de 6 mois et les facteurs associés avec le non achèvement.Schéma : Etude rétrospective de cohorte.Résultats : Sur 578 patients, 466 (81%) ont achevé le TPI. Sur 112 patients qui n'ont pas achevé le TPI, 69 (60%) ont été perdus de vue, 30 (27%) ont arrêté le traitement sans raison documentée, 8 (7%) ont eu des problèmes de toxicité/d'effets secondaires, 5 (5%) ont eu un problème documenté de rupture de stock et le reste a déménagé ou refusé de continuer le traitement. Les facteurs associés avec un risque plus faible de ne pas achever le TPI ont été le fait d'être parallèlement sous traitement antirétrovirale (TAR) (odds ratio ajusté [ORa] 0,09 ; IC95% 0,03­0,28) et le fait de recevoir plus de 2 mois de stock d'isoniazide au début du traitement, tandis que l'absence aux rendezvous de consultation avant la mise en route du TPI (ORa 5,25 ; IC95% 2,10­13,14) a été associé avec un risque plus élevé de non achèvement.Conclusion : Les taux d'achèvement du TPI dans sept sites pilotes du Zimbabwe ont été comparativement élevés, ce qui montre que le déploiement du TPI dans des structures de santé publique est faisable. Une amélioration des conseils en vue de l'adhésion ou une recherche active des patients avant le TAR et de ceux qui ont des antécédents d'abandon, ainsi qu'une synchronisation des fournitures de TPI et de TAR, pourraient améliorer les taux d'achèvement.

Marco de referencia: Siete establecimientos en Zimbabue que participaron en un ensayo preliminar del tratamiento preventivo con isoniazida (TPI) de 6 meses en personas viviendo con el virus de la inmunodeficiencia humana (PVVIH).Objetivo: Determinar las tasas de finalización del TPI de 6 meses de duración y los factores que se asocian la falta de compleción del mismo en las PVVIH.Método: Un estudio retrospectivo de cohortes.Resultados: De los 578 pacientes estudiados, 466 terminaron el ciclo de TPI (81%). De 112 pacientes que no completaron el tratamiento, 69 se perdieron durante el seguimiento (60%), 30 interrumpieron el tratamiento sin que exista un registro de la razón (27%), 8 presentaron reacciones tóxicas o efectos adversos de los medicamentos (7%), en 5 se registró un desabastecimiento de medicamentos (5%) y los demás se transfirieron a otros centros o rehusaron la continuación el tratamiento. Los factores asociados con un menor riesgo de no completar el TPI fueron el hecho de estar recibiendo tratamiento antirretrovírico (TAR) (cociente de posibilidades ajustado [ORa] 0,09; intervalo de confianza [IC] del 95% 0,03­0,28) y el hecho de recibir una reserva de isoniazida para ⩾2 meses al comienzo del ciclo, y el factor que se asoció con un mayor riesgo de no finalizar el tratamiento fue cuando el paciente había incumplido citas médicas antes de comenzar el tratamiento (ORa 5,25; IC95% 2,10­13,14).Conclusión: Las tasas de finalización del TPI en los siete centros pilotos de Zimbabue fueron relativamente altas e indican que es factible desplegar esta iniciativa en los establecimientos públicos de salud. Es posible mejorar las tasas de finalización con un refuerzo de la orientación sobre la observancia terapéutica, el seguimiento activo de los usuarios que no han iniciado el TAR y los que tienen antecedentes de incumplimiento y con la sincronización del reaprovisionamiento del TPI y el TAR.

Morbidity and mortality patterns in HIV-1 seropositive/ seronegative women in Kampala and Harare during pregnancy and in the subsequent two years.

OBJECTIVE: To compare birth outcomes, hospital admissions and mortality amongst HIV-1 seropositive and HIV-1 seronegative pregnant women in Kampala, Uganda and Harare, Zimbabwe. DESIGN: In Kampala and Harare about 400 HIV-1 seropositive and 400 HIV-1 seronegative pregnant women were recruited at initial visit for antenatal care into a prospective study and followed for two years after delivery. The women were classified as HIV-1 seropositive at recruitment if initial and second ELISA tests were positive and confirmed by Western Blot assay. Data on demographic, reproductive, contraceptive and medical histories were obtained using a comprehensive questionnaire at entry, 32 and 36 weeks gestation, at delivery and at six, 12, and 24 months post delivery. In addition, a physical examination and various blood tests were performed at each antenatal and post natal visit. RESULTS: During the two years after delivery, HIV-1 seropositive women had higher hospital admission and death rates than HIV-1 seronegative women. HIV-1 seropositive mothers had a two-fold increase in risk of being admitted to hospital (Kampala: RR = 2.09; 95% CI = 0.95 to 4.59; Harare: RR = 1.98; 95% CI = 1.13 to 3.45). In the six weeks after delivery eight deaths occurred, six of which were among HIV-1 seropositive women and in the period from six weeks to two years after delivery, 53 deaths occurred, 51 of which were among HIV-1 seropositive women (Kampala: RR = 17.7; 95% CI = 4.3 to 73.2; Harare: RR = 10.0; 95% CI = 2.3 to 43.1). However, there was no difference in hospital admission rates between HIV-1 seropositive and seronegative women during pregnancy itself and there was only one death during that period (in a HIV-1 seronegative woman). There was no difference in the frequency of complications of delivery between HIV-1 seropositive and HIV-1 seronegative women and the outcome of births were also similar. CONCLUSIONS: A significant number of HIV-1 positive pregnant women presented at both Harare and Kampala although there was no difference in the number of hospital admissions or mortality between HIV-1 seropositive and HIV-1 seronegative women during pregnancy. Although there were no differences in complications during pregnancy or outcome at delivery, in the two years after delivery, HIV-1 seropositive women in both centres were at increased risk of being admitted to hospital and of dying.

Risk factors for high diarrhoea frequency: a study in rural Zimbabwe.

Diarrhoea morbidity data were collected prospectively over 22 months from a cohort of young children living in a deprived community in rural Zimbabwe. Despite the general high prevalence of diarrhoeal disease, there was considerable individual variability in attack rates. Risk factors associated with high diarrhoea frequency were therefore sought by a questionnaire study on feeding, environmental, educational and socio-economic factors. This was supported by observation of living conditions, and water and sanitation facilities. Surprisingly, no association was found between diarrhoeal morbidity and any of these factors, suggesting that other factors such as individual hygiene behaviour or individual susceptibility to diarrhoea may play a role in determining the observed differences in diarrhoea rates in this community.

Diarrhoea and growth faltering in rural Zimbabwe.

OBJECTIVE: To assess the evidence that diarrhoea is an important cause of growth faltering in young children in developing countries. DESIGN: Prospective, longitudinal cohort study. SETTING: Worker's compounds on commercial farms in Shamva, rural Zimbabwe. SUBJECTS: 204 children < 12 months old were enrolled, 73 from birth. The median age at enrolment was 4 months. Eleven children died and 39 were lost to follow-up. INTERVENTIONS: Prospective weekly diarrhoea surveillance by farm health workers and monthly anthropometry. RESULTS: Growth faltering was severe, but there was little difference in average rates of growth between children with frequent diarrhoea and infrequent diarrhoea. The results of an interval-based data analysis were consistent with there being only a transient effect of diarrhoea on weight gain. Estimation of weight faltering following episodes of diarrhoea and the rate of return to the trend in the 9-14 month age range, indicated that weight loss associated with each episode was small (approximately 2%) and return to the child's trend was 90% complete within a month. At older ages than this, weight loss appeared to be less, and estimates were not statistically significant. CONCLUSIONS: These observations lend weight to the hypothesis that recurrent episodes of diarrhoea are not a potent cause of growth faltering in early childhood except in a small minority of largely catastrophic cases. Inadequate food intake is a more plausible explanation.

PIP: In Zimbabwe, health workers collected data on diarrhea incidence every week and anthropometric data once a month from 204 children aged less than 12 months to examine the association between diarrhea and growth faltering. 73 children were enrolled at birth. 148 children were followed throughout the entire study. 11 children died (8 because of diarrhea or protein-energy malnutrition). 39 children were lost to follow-up. The children's parents were farm laborers who lived on large-scale commercial farms in Shamva district. Diarrhea incidence peaked between 13 and 18 months. In 91% of attacks, the diarrhea was watery rather than bloody. 31 children had more than 9 diarrhea episodes (high diarrhea frequency). 25 had no more than 4 diarrhea episodes (low diarrhea frequency). There was little difference in the children's mean weight and mean length from 1 to 30 months of age between high and low diarrhea frequency subjects. The average loss of overall growth per diarrhea episode in the age range 9-23 months was 51 g and 0.18 cm. In the age range of 9-14 months, weight loss after the diarrhea episode was 2.3% of body weight, and 90% of the sudden weight decline below the child's trend was recovered in 30 days. Weight loss was less than 2.3% among older children. A 2.3% weight loss in an 8 kg child is 180 g. Assuming that diarrhea is responsible for the entire weight loss (about 66 g/episode), the reduction in overall growth is about 120 g (1.5%). The total energy needed to accumulate 120 g is 480 kcal; thus, a child would require an additional 2-3 kcal/kg/day (a small amount) to gain 120 g. These findings support the hypothesis that recurrent diarrhea episodes do not induce growth faltering except in a few cases. Inadequate food intake is a more plausible explanation.

Clinical evaluation of Nutrition Mix-1.A. Dietary supplement in sick and undernourished children.

Eight hundred and forty children between the ages of 12 and 36 months were given approximately six g daily as a supplement to their normal daily diet, of Nutrition Mix-1 for an average of 10 months each. Nutrition Mix-1(NM-1) is not a breast milk substitute, feeding formula nor a weaning food on its own. Four hundred and sixty children (54.8 pc) suffered from HIV-related disease, 280 children had several episodes of childhood diseases (33.3 pc) among whom 120 suffered from PEM. One hundred children were normal and healthy. All the children gained weight during the study period. The average weight gain was 25.7 pc for the sick and 26.8 pc the PEM children, 26.0 pc for the normal children and 51.2 pc for the HIV-related disease (HIV-RD) children-paediatric AIDS. It is concluded that NM-1 when used as recommended, is a very useful supplement for balancing children's diet in the developing or Third world countries.

Breastfeeding: breast milk banks and human immunodeficiency virus.

HIV in infants and children in Zimbabwe is virtually limited to vertical transmission. Less than 5 cases of transfusion acquired HIV infections have been documented to date. Zimbabwe was the third country in the world after the United States, to screen transfusion blood and blood products. The controversy of HIV transmission through breast milk is still far from resolved. In developing countries, breast-milk substitutes for formulae are not only prohibitively expensive but dangerous because of unhygienic and economic constraints. The paper argues the case for continued breast-feeding of infants by their HIV seropositive mothers.

PIP: A pediatrician at the University of Zimbabwe Medical School in Harare reviewed 3 HIV related cases of perinatal transmission and breast feeding. The 1st case was born to a mother with AIDS who died 1 week later. Her HIV negative sister breast fed the infant along with her own. The surrogate mother, her husband, and her child tested HIV negative. The baby tested HIV positive, however. The 2nd case included a mother who delivered twins--1 vaginally and the other by cesarean section. The vaginally delivered twin developed AIDS. The parents did not know until symptoms appeared in this twin that they were infected with HIV. The twin delivered by cesarean section continuously tested HIV seronegative. In the 3rd case, an HIV positive mother began breast feeding another woman's child at 1 month. Her own infant also tested HIV positive. After 24 months, the surrogate child remained HIV negative. These cases and current knowledge of HIV indicated that the risk of HIV transmission via breast milk is extremely low. Nevertheless researchers need to conduct prospective studies of infants born to HIV positive mothers in Africa to determine actual risk of transmission by breast milk. This type of transmission is dependent on the status of the disease in the mother, health and nutritional status of surrogate mothers, circumstances of childbirth, and AIDS acceleration factors such as malnutrition and viral load. Heating breast milk to 57.5 degrees celsius for 30-33 minutes deactivated the reverse transcriptase needed for replication of HIV. Moreover heating does not alter the promotive and promotive and protective properties of breast milk. Therefore pooled or banked breast milk is an alternative, but there is emotional resistance to breast milk banks. Yet developing countries cannot afford the alternative, formula. So breast feeding or breast milk is the only practical means to feed infants.

Clinical presentation of symptomatic human immuno-deficiency virus in children.

PIP: The predominantly heterosexual transmission of human immunodeficiency virus (HIV) in Africa suggests that pediatric acquired immunodeficiency syndrome (AIDS) could develop into a significant child health problem in this region. To assist clinicians in recognizing HIV infection in African children, the clinical features of 185 children with symptomatic HIV-related disease diagnosed at the 2 central hospitals in Harare, Zimbabwe, from April 1986-July 1987 were enumerated. In this period, 185 such cases were diagnosed. 83 (47%) involved children 0-12 months of age and another 61 (35%) represented children 13-24 months old. The male/female ratio was 1.0:1.03. The most frequently recorded clinical feature (52% of cases) was generalized lymphadenopathy, with or without hepatosplenomegaly. 45% of HIV-infected children presented with respiratory symptoms and pulmonary infiltrates on chest x-ray. Failure to thrive was present in 38% of cases. Also relatively common were hepatomegaly and splenomegaly (35% and 26%, respectively). Chronic, recurrent diarrhea was present in 21%. Less frequently observed (under 10% of cases) clinical findings were maculopapular eczematoid rashes, parotid swelling, chronic suppurative otitis media, chronic mucopurulent rhinitis, meningitis, and encephalopathy. 3 main clinical modes of presentation were identified--children with failure to thrive or marasmus in association with chronic diarrhea and developmental delay, those with generalized lymphadenopathy and hepatosplenomegaly, and children who present with chronic cough with pulmonary infiltrates on chest x-ray.^ieng

Early growth faltering in rural Zimbabwean children.

Longitudinal data on weight and height were collected during the first 30 months of life from children living in a deprived rural community in Zimbabwe. All were breast-fed for up to a mean of 21 months; maize porridge being introduced from three months onwards. During the first 6 months, growth was similar to, or even exceeded, that of the NCHS reference population. Thereafter, growth faltering was common. By the age of 30 months, there was a mean deficit in weight of 2,0 kg in girls and 2,3 kg in boys, and a mean deficit in height of 8 cm in boys and 9 cm in girls. No seasonal variation in growth pattern was found. The substantially better growth of more privileged children in Zimbabwe and elsewhere in Africa, would suggest that these children were failing to realise their full genetic potential for growth because of adverse environmental factors.

Lighting a dark corner.

PIP: In Karanga community, 410 km south of Harare, Zimbabwe, the Intermediate Technology Development Group's (ITDG) farming project has successfully improved household food security through its farming project. The ITDG encouraged the formation of 35 women's garden clubs that have allowed women to reduce their individual labor, become closer to each other, and incorporate improved farming methods to increase crop production. The ITDG started work in 1991, just before a severe drought in 1992 forced over 770,000 people to rely on aid for food. ITDG changed the unsuccessful, top-down approach of state agricultural workers to a more successful, bottom-up approach. It also reintroduced intercropping and integrated farming systems to compensate for the fact that the average number of households of six people manages with only about a hectare of land. Indigenous methods, such as intercropping onions for pest management, are reducing reliance on chemicals, and chicken and goal manure is used for fertilizer. In addition to improving food security and nutrition, the gardens are producing enough surplus vegetables for sale. ITDG has also assisted the drought-prone community in developing water conservation techniques that use infiltration pits and gravity to nourish the soil after the rains have stopped.^ieng

Why mother's milk is best.

PIP: Breast milk substitutes made of water, porridge, or animal milk were given to babies only as a life-saving effort prior to World War II, in the event of lack of mother's milk, breast infection or the death of the mother. In the post-war era of the early 1950's, improperly constituted infant formulas became prevalent in the industrialized world to allow the release of women into the work force. Advertising and marketing techniques were also launched in Third World countries, which became easy victims of this ploy because of ignorance, poverty, and inadequate sanitation. Medical consequences include infections from contamination at the source (infantile botulism); hyponatremia, hypocalcaemia, with poor muscle, heart, and brain functioning, from over dilution with water; and infectious diarrhea, which can lead to marasmus and kwashiorkor, from mixture contaminated water. Breast milk contains colostrum, a supercharged nutrient that ensures meeting the infant's immediate energy needs as well as providing antibodies to most childhood diseases. Infant formulas cannot provide this protection. The introduction of weaning foods occurs around 5-6 months of age, when local foodstuffs rather than commercial supplements ought to be used. However, semi-literate mothers are often exposed to radio advertising about substitutes that overwhelm them. Their infants get formula diluted in unclean water and unsuitable solids too early. They will eventually live on fresh cow's milk with the attendant problems of anemia and bovine tuberculosis. Breast-feeding also provides a practical means of birth control and child spacing. The government should enact a national code on the manufacture, nutritional contents, and sale of these substitutes.^ieng

Recurrent and persistent diarrhoea in a rural Zimbabwean community: a prospective study.

Prospective surveillance of patterns of diarrhoeal disease was conducted in a cohort of 204 young children living in a rural community in Zimbabwe. Trained field assistants recorded morbidity data obtained by weekly recall of mothers. Diarrhoea was defined by a commonly used local word, and a diarrhoea-free gap of three or more days was taken to signify a new attack. Diarrhoea was common in this study population with a peak incidence between 6 and 18 months of age. There was, however, wide individual variability in diarrhoea attack rates (range 0 to 20 attacks) during the 22 month study period. Whilst only 6 per cent of the recorded diarrhoea episodes were persistent (lasting longer than 14 days), a high proportion (26 per cent) of subjects had at least one attack of persistent diarrhoea (PD) during follow up. Children who had frequent attacks of acute diarrhoea also tended to have PD; PD was rare in those with few attacks. Thus, within this uniformly deprived African community, there were individuals who had a much higher susceptibility to diarrhoea compared to others. An understanding of this variability may point the way towards more effective interventions in the control of diarrhoeal disease.